Quick Crams

Question 1

NNT

Answer 1

= 1/ARR (absolute risk reduction - ALSO KNOWN AS RISK DIFFERENCE or attributable risk)

ARR = (control event rate) - (experimental event rate)

Question 2

Weight

Answer 2

= (age +4) x2

Question 3

Bioavailability

Answer 3

= AUC(oral) / AUC(IV)

Question 4

Volume of distribution

Answer 4

= Dose(IV) / plasma concentration

Question 5

Mid parental height

Answer 5

= (M+F +/- 13) / 2

Range +/- 8cm

Question 6

Height velocity

Answer 6

= difference b/w 2 heights divided by time x12 (measured per year)

Question 7

Likelihood ratios

Answer 7

Positive = sens/(100%-spec)
Negative = (100-sens)/spec

Question 8

Mixed venous sats

Answer 8

= (3xSVC)+(1xIVC) / 4

Question 9

Qp:Qs

Answer 9

= (Ao sats - MV sats) / (PV sat - PA sat)

Question 10

Pressure conversion mmHg and kPa

Answer 10

7.5

I.e. 100 kPa = 750mmHg

Question 11

Osmolarity

Answer 11

= 2xNa + glucose + urea

Question 12

Urine anion gap

Answer 12

= Na + K - Cl

Gap influenced by ammonium = positively charge. Therefore if gap negative, suggests high urinary ammonium, suggests kidneys can secrete H+ (i.e. not distal/type1 RTA).

Question 13

Insensible losses

Answer 13

= 400mL/m^2/day

Question 14

eGFR

Answer 14

= 36.5 x height(cm) / creatinine

Question 15

CYP450 inducers

Answer 15

CRAP GPS

Carbamazepine (can autoinduce), rifampicin, alcohol, phenytoin, griseofulcin, phenobarbitone, sulfonyluea

Question 16

CYP450 inhibitors

Answer 16

SICKFACES.COM

Sodium valproate, isoniazid, cimetidine, ketoconazole, fluconazole, alcohol, chlorampheicol, erythromycin, sulfonamide, ciprofloxacin, omeprazole, metronidazole

Question 17

ABCB4

Answer 17

PFIC3 - MDR3 deficiency

Question 18

EPCAM

Answer 18

Tufting enteropathy

Lynch syndrome

Question 19

JAG1

Answer 19

Alagille’s

Also NOTCH2 but less common

Question 20

MYO5B

Answer 20

Microvillus inclusion disease

Question 21

NOD2

Answer 21

IBD/Crohn’s

Question 22

SERPINA1

Answer 22

A1AT

Question 23

ATP7B

Answer 23

Wilson’s disease

Question 24

HRAS

Answer 24

Costello syndrome

Question 25

APC

Answer 25

Familial adenomatous polyposis

Question 26

STK11

Answer 26

Peutz Jeghers syndrome

Question 27

RET

Answer 27

Hirschprungs

Question 28

UGTP81

Answer 28

Gilberts

Question 29

SBDS

Answer 29

Shwachmann Diamond syndrome

Question 30

UGTA1A

Answer 30

Crigler Najjar

Question 31

FOXP3

Answer 31

IPEX

Question 32

SCL5A1

Answer 32

Glucose galactose malabsorption

Question 33

ALDOB

Answer 33

Hereditary fructose intolerance

Question 34

MECP2

Answer 34

Rett syndrome

Question 35

FBN1

Answer 35

Marfan syndrome | Fibrillin 1

Question 36

COL2A1

Answer 36

Stickler syndrome

Question 37

NSD1

Answer 37

Sotos syndrome

Question 38

SCN1A

Answer 38

Dravet syndrome | Genetic epilepsy with febrile seizures plus

Question 39

KCNQ2 and 3

Answer 39

Benign familial neonatal convulsions

Question 40

CYP21A and B

Answer 40

21 hydroxylase deficiency -> CAH

Question 41

SHOX

Answer 41

Short stature homeobox On X and Y chromosomes Relevant for height in Turner, Klinefelter, etc

Question 42

SPRED1

Answer 42

Legius syndrome

Question 43

Causes pancreatic insufficiency

Answer 43

CF Shwachmann Diamond Pearson Johanson-Blizzard

Question 44

Hyperammonaemia acute treatment

Answer 44

Benzoate

Question 45

Radial ray syndromes

Answer 45

``` Cornelia de Lange Fanconi anaemia Holt Oram T18 (Edward) VACTERYL Others ```

Question 46

Jervell LangeNeilsen syndrome

Answer 46

AR Long QT with congenital SNHL/deafness

Question 47

Anticholinergic antidote

Answer 47

Physostigmine | Supportive

Question 48

Cholinergic antidote

Answer 48

Atropine

Question 49

Sympathomimetic/amphetamine antidote

Answer 49

Supportive Adrenergic blocker but avoid BB Benzos Dantrolene

Question 50

NMS antidote

Answer 50

Bromocriptine Amantadine Dantrolene

Question 51

Serotonin syndrome antidote

Answer 51

Cyproheptadine Olanzapine Benzos

Question 52

Benzos antidote

Answer 52

Flumazenil

Question 53

Iron antidote

Answer 53

Desferrioxamine

Question 54

Isoniazide antidote

Answer 54

Pyridoxine /B6

Question 55

Malignant hyperthermia antidote

Answer 55

Dantrolene

Question 56

Methaemoglobinaemia antidote

Answer 56

Methylene blue | Ascorbic acid

Question 57

Opioid antidote

Answer 57

Naloxone

Question 58

Paracetamol antidote

Answer 58

N acetyl cysteine

Question 59

Sulphonylurea antidote

Answer 59

Octreotide

Question 60

TCA antidote

Answer 60

Sodium bicarbonate

Question 61

Warfarin antidote

Answer 61

Vitamin K FFP Prothrombinex

Question 62

CCB antidote

Answer 62

Calcium | High dose insulin therapy

Question 63

Dystonic reaction antidote

Answer 63

Benztropine | Diphenhydramine

Question 64

Beta blocker antidote

Answer 64

Adrenaline High dose insulin therapy Calcium

Question 65

Ethylene glycol antidote

Answer 65

Ethanol

Question 66

Bupivacaine / local anaesthetic antidote

Answer 66

Intralipid

Question 67

Hypertensive crisis antidote

Answer 67

Nitroprusside

Question 68

SOS/VOD treatmetn

Answer 68

Defibrotide

Question 69

Components cryoprecipitate

Answer 69

VWF, F8, fibronigen

Question 70

Invasive pneumococcal infection <2yo/neonates

Answer 70

Consider toll like receptor defect

Question 71

Recurrent Neisseria

Answer 71

Complement defect, MAC

Question 72

Recurrent sinopulmonary infections

Answer 72

B cell defect or complement defect

Question 73

Inability of B cells to differentiate into plasma cells capable of secreting all immunoglobulin types

Answer 73

Characteristic feature of CVID

Question 74

Male neonate with encephalopathy and respiratory alkalosis

Answer 74

UCD/OTC

Question 75

Normal distribution standard deviations

Answer 75

``` 1 = 68% of population 2 = 95% 3 = 99.7% ```

Question 76

Penicillin MOA

Answer 76

Block ability to cross link peptidoglycan polymers, inhibit cell wall synthesis

Question 77

Vancomycin MOA

Answer 77

Bind terminal D-alanyl-D-alanine residues during cell wall synthesis

Question 78

Ciprofloxacin MOA

Answer 78

Fluoroquinolone Inhibits DNA gyrase Resistance via efflux pump, proteins that bind and protect DNA gyrase, reduced affinity to quinolones

Question 79

Aminoglycoside MOA

Answer 79

Bind 30S subunit | Prevent 50S subunit binding, therefore no protein synthesis

Question 80

Macrolide MOA

Answer 80

Reversible binding 50S subunit | Prevent joining/binding amino acids together

Question 81

Tetracycline MOA

Answer 81

Reversible binding 30S subunit | Prevent tRNA alignment

Question 82

TMP/SMX MOA

Answer 82

Block folinic acid synthesis

Question 83

Nitrofurantoin MOA

Answer 83

Damages bacterial DNA

Question 84

DIOS treatment

Answer 84

Oral gastrografin | Others

Question 85

Myopia, risk of retinal detachment, SNHL, MVP, joint hypermobility

Answer 85

Stickler syndrome COL2A1 Abnormal production/assembly collage type 2

Question 86

Unibrow, arched eyebrows, long eyelashes, hirsuit, ulnar ray defects

Answer 86

Cornelia de Lange

Question 87

4-10yo with overgrowth and mild ID

Answer 87

Sotos syndrome | Homocysteinuria as well, but have ectopia lentis (down), stiff joints

Question 88

Reactive arthritis, urethritis/balanitis/cystitis, conjunctivitis

Answer 88

Reiter syndrome

Question 89

Recurrent aphthous ulcers, genital ulcers, uveitis

Answer 89

Behcet syndrome

Question 90

AR periodic fever syndromes

Answer 90

FMF | Hyper IgD with period fevers

Question 91

FMF

Answer 91

Recurrent short 1-3 day self limited episodes of fever, serositis, arthritis, rash (classically ankle/dorsum foot). Variable frequency, weeks to years. Colchicine Amyloidosis is most serious complication

Question 92

HIDS

Answer 92

<6mp Fever 3-7 days, N/V/D, abdo pain (+/- LN, rash, arthritis, splenomegaly) Improve with age

Question 93

TRAPS

Answer 93

Tumour necrosis factor receptor associated periodic syndrome Episodes of: fever, abdo pain, myalgia, rash, conjunctivitis, chest pain, arthralgia Last >5 days, can last weeks Steroids, not colchicine

Question 94

PFAPA

Answer 94

Periodic fever, aphthous stomatitis, pharyngitis, adenitis. Most common recurrent fever syndrome in children. 2-5yo 4-6 days, every 3-6 weeks like clockwork Improve with age Dramatic response to pred

Question 95

Raised homocysteine

Answer 95

B12 or folate deficiency B12 has raise methylmalonic acid as well May be other causes

Question 96

Pasturella

Answer 96

Type of bacteria | Animal bites, e.g. dogs (canis), cats (mulocida)

Question 97

Fanconi syndrome causes

Answer 97

Acquired: drugs (aminoglycosides, cisplatin, ifosfamide, valproate, deferasinox), metals (lead, mercury, cadmium), vitamin D disorders Congenital: Dent, cystinosis, tyrosinemia, galactosemia, Wilsons, hereditary fructose intolerance, mitochondrial myopathies

Question 98

Central causes precocious puberty

Answer 98

Hypothalamic hamartoma (most common, a/w gelastic seizures), severe untreated hypothyroidism, other brain tumours, hydrocephalus, head trauma

Question 99

CD40L

Answer 99

``` Hyper IgM syndrome Needed for class switching ```

Question 100

WASP gene

Answer 100

Wiskott Aldrich syndrome protein

Question 101

BTK

Answer 101

X-linked agammaglobulinaemia | Bruton tyrosine kinase

Question 102

Sweaty sock odour

Answer 102

Isovaleric acidaemia

Question 103

NST Victoria conditions

Answer 103

Condition Synonyms 3-hydroxy-3-methylglutaryl CoA lyase HMG CoA lyase 3-methylglutaryl CoA hydratase 3-methylglutaconic aciduria type 1 Argininosuccinic aciduria Argininosuccinate lyase Citrullinaemia type 1 Argininosuccinate synthetase Beta ketothiolase T2 deficiency, 3-oxothiolase Maple syrup urine disease MSUD, branched chain keto acid dehydrogenase (mild/intermittent forms may not be detected) Carnitine palmitoyl transferase 1 CPT1 Carnitine palmitoyl transferase 2 CPT2 Carnitine uptake defect CUD, systemic carnitine deficiency, carnitine transporter defect, OCTN2 defect 2 Carnitine-acyl carnitine translocase CACT Cobalamin disorders cblC, cblD, cblF disease Cystic fibrosis CFTR Homocystinuria Cystathionine betasynthase, CBS (vitamin responsive forms may not be detected) Hypothyroidism Glutaric aciduria type 1 Glutaryl CoA dehydrogenase, GA1 Holocarboxylase synthase HCS, multiple carboxylase deficiency, MCD Isovaleryl CoA dehydrogenase Isovaleric acidaemia, IVA Medium-chain acyl CoA dehydrogenase MCAD Methylmalonic acidaemia Methylmalonyl CoA mutase, MMA, cblA, cblB disease Mitochodrial trifunctional protein Long-chain hydroxy acyl carnitine dehydrogenase, LCHAD, MTP Multiple acyl CoA dehydrogenase MADD, glutaric aciduria type 2, GA2, ETF deficiency Phenylketonuria PKU, phenylalanine hydroxylase, including tetrahydrobiopterin defects Propionic acidaemia Propionyl CoA carboxylase, PA, ketotic hyperglycinaemia Tyrosinaemia 2 Tyrosine aminotransferase Very long chain acyl CoA dehydrogenase VLCAD

Question 104

Cystinosis treatment

Answer 104

Cysteamine

Question 105

Apert syndrome

Answer 105

Acrocephaly, facial underdevelopment, syndactyly, learning disability. Acrocephaly = oxycephaly = high pointed head, sutures involved coronal sagittal and lambdoid. More severe than Crouzon

Question 106

Crouzon syndrome

Answer 106

Acrocephaly, scaphocephaly, or brachycephaly Hypertelerosim, exophthalmos, increased ICP, learning disability. Milder than Apert

Question 107

Sacphocephaly

Answer 107

Elongated narrow skull | Sagittal suture

Question 108

Brachycephaly

Answer 108

Short, broad skull | Both coronal sutures involved

Question 109

Plagiocephaly

Answer 109

Unilateral flattening of skull | Single coronal suture, occasionally lambdoid

Question 110

Trigonocephaly

Answer 110

Narrow, pointed forehead | Metopic suture involved

Question 111

Kleeblattschädel

Answer 111

Also known as cloverleaf deformity, occurs when multiple sutures fuse prematurely. The coronal, lambdoid, and metopic sutures are most frequently affected. Bulging of the skull through the open sagittal and temporosquamosal sutures produces a trilobate skull. Kleeblattschädel is a rare anomaly, with fewer than 130 cases reported in the literature. Kleeblattschädel is the most severe form of cranial dysostoses. Nearly all affected patients have hydrocephalus and intellectual disability.

Question 112

Craniosynostosis syndromes

Answer 112

``` Apert Crouzon Pfeiffer Carpenter SAETHRE-CHOTZEN SYNDROME ```

Question 113

COL1A1 and 2

Answer 113

``` Osteogenesis imperfecta Treat with bisphosphonates Clinical features: Fractures with minimal or no trauma Dental abnormalities (dentogenesis imperfecta) Hearing loss Blue sclerae Osteoporosis Wormian bones (extra bones within cranial sutures) ```

Question 114

Interrupted eyebrows

Answer 114

Kabuki syndrome

Question 115

Shwachman Diamond Syndrome

Answer 115

``` GIT ***Pancreatic Insufficiency*** Hematological ***Bone Marrow Failure*** Malignancy: AML ``` Exocrine pancreatic dysfunction, cytopenias, and abnormalities of bone

Question 116

USH2A

Answer 116

Usher syndrome Genetic disorder affecting the cochlear and retina Most common form of syndromic retinitis pigmentosa (2nd most common = Bardet-Biedl)

Question 117

TCOF1

Answer 117

Treacher Collins

Question 118

Types/causes of shock

Answer 118

Hypovolaemic (haemorrhage, gastroenteritis, intussusception, burns) Distributive (septicaemia, anaphylaxis, spinal cord injury e.g. neurogenic) Cardiogenic (arrhythmia, heart failure, valve disease) Obstructive (congenital cardiac, tension pneumothorax, flail chest, tamponade, PE) Dissociative (profound anaemia, carbon monoxide poisoning, methaemoglobinaemia)

Question 119

Eikenella corrodens

Answer 119

Human bites (30%) GN rod, normal mucosal commensal, hard to grow. Penicillin, 3rd gen cephalosporin

Question 120

Toxidromes - sympathomimetic

Answer 120

Amphetamines: MDMA, ecstasy, meth, ice Cocaine, caffeine Ritalin, LSD, theophylline Everything up: tachycardic, tachypnoeic, hypertermic, dilated pupils (reactive), increased bowel sounds, diaphoresis CF anticholingeric: no diaphoretic, reduced bowel sounds, urine retention

Question 121

Toxidromes - anticholinergic

Answer 121

Examples: atropine, antihistamines, amitriptyline Tachycardic, hyperthermic, dilated pupils Reduced bowel sounds, normal RR, dry/no diaphoresis Non reactive pupils Picking behaviours

Question 122

Toxidromes - serotonin syndrome

Answer 122

Examples: TCA, MAOI, SSRI, St Johns Wart, amphetamines, tramadol CLONUS Abrupt onset, rapidly resolving, myoclonus+tremor, hyperreflexia, mydriasis (dilated - d for dilated)

Question 123

Toxidromes - neuroleptic malignant syndrome

Answer 123

Neuroleptics = antipsychotics, especially haloperidol Life threatening idiosyncratic reaction due to dopamine blockade Gradual onset usually 4-14 days, prolonged course Fever, diaphoresis, unstable BP, altered conscious state, rigidity (diffuse) Hyporeflexia Normal pupils

Question 124

Toxidromes - cholinergics

Answer 124

E.g. organic phosphorous compounds, nerve agents, nicotine poisoning, poisonous fungi miosis, increased bowel sounds, diaphoresis NORMAL HR, RR, temperature Treat with atropine

Question 125

Toxidromes - opioids

Answer 125

Bradycardia, bradypnoea, hypothermia, miosis, reduced bowel sounds, dry/no diaphoresis

Question 126

Toxidromes - TCA

Answer 126

Sedation, coma, seizure, hypotension, tachycardia BROAD QRS Anticholinergic syndrome can occur too Treat with sodium bicarbonate

Question 127

Toxidromes - BB or CCB

Answer 127

Bradycardia, hypotension, reduced conscious state

Question 128

Activated charcoal - indications, contraindications

Answer 128

(RCH guideline) List of selected toxins where activated charcoal may be considered: Amisulpride Chloroquine, hydroxychloroquine or quinine Calcium channel blockers, particularly verapamil and diltiazem Carbamazepine Colchicine Beta Blockers Flecainide Methotrexate Paraquat/diquat ``` List of toxins where Charcoal is NOT helpful and contraindicated: Acid and Alkalis / corrosives Cyanide Ethanol/methanol/glycols Eucalyptus and Essential Oils Fluoride Hydrocarbons Metals - including Lithium, Iron compounds, potassium, lead Mineral acids - Boric acid ``` Adverse Effects: Respiratory - aspiration, progressive respiratory failure; Death. Beware oral use with drowsiness, or following the ingestion of substances which could cause rapidly reduced CNS depression or may cause seizures Faecal discolouration GI obstruction: by bezoar formation

Question 129

Brugada syndrome

Answer 129

Due to a mutation in the cardiac sodium channel gene RBBB V1-3 with STE and negative T wave Tachyarrhythmia from fever - may mimic febrile convulsion SCD a/w sleep/fever Treat with ICD

Question 130

VACTERL association

Answer 130

V – vertebral (60-80%, fused, misshapen, additional vertebra) A – anal (90% - anal atresia) C – cardiac (40-80%) VSD most common T – trachea-oesophageal fistula (50-80%) R – renal (50%, most common = renal agenesis) L – limb (50%, missing thumb or poorly developed forearms/hands) Can occur with Fanconi anaemia

Question 131

CHARGE syndrome

Answer 131

C – Coloboma H – Heart anomalies Most common: TOF*, ASD, AVSD, arch A – choanal Atresia R – Retardation of growth/development (ID) G – genital anomalies (unilateral renal agenesis, renal hypoplasia, duplex kidney, UPJO or VUR) E - Ear anomalies (asymmetric, small, cup-shaped, wide helix) Caused by mutations of CHD7 on chromosome 8q12.

Question 132

APECED

Answer 132

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Due to mutations in AIRE gene (important for synthesis of autoimmune regulator protein) Classic triad: Mucocutaneous candidiasis (presenting ft in 60%, all will have by age 40) Hypoparathyroidism (30% initially, 80% eventually affected) Hypocalcemia and hypomagnesemia can be difficult to control -> seizures Adrenal failure (5% at presentation, 60% by age 15)

Question 133

Albright hereditary osteodystrophy

Answer 133

Type 1a pseudohypoparathyroidism Loss of function mutation of GNAS1 (PTH receptor) Requires maternal transmission for expression GNAS1 is also expressed in the thyroid, gonads and pituitary glands

Question 134

Wolfram syndrome

Answer 134

AKA DIDMOAD | = diabetes insipidus, diabetes mellitus, optic atrophy and deafness

Question 135

Evan’s syndrome

Answer 135

Auotimmune haemolytic anaemia (AIHA) + immune thrombocytopenia (ITP) and/or autoimmune neutropenia Accounts for 15-30% of paediatric AIHA Prognosis: more difficult to treat than AIHA alone and tends to have a chronic relapsing course No specific underlying defect identified Presentation: Typically present with AIHA and then develop additional cytopenias months-years later Or present with ITP and subsequently develop AIHA

Question 136

Kawasaki criteria

Answer 136

``` Fever 5+ days, with 4/5: Conjunctivitis Rash Oral changes Extremity changes Lymphadenopathy ```

Question 137

Jones criteria

Answer 137

For rheumatic fever ``` MAJOR Carditis Polyarthritis Chorea, Sydenhams Erythema marginatum Subcutaneous nodules ``` MINOR Fever, polyarthralgia Raised CRP/ESR Prolonged PR on ECG Supporting evidence of preceding strep infection w/i 45 days.

Question 138

Cytokine release syndrome

Answer 138

Acute systemic inflammatory syndrome, fever and multiple organ dysfunction, d/t: CAR-T cell therapy, monoclonal antibodies, haploidentical allogenic transplant Essentially an extreme infusion reaction. Usually within 2-3 days of inciting agent, but up to 2 weeks.

Question 139

Fanconi anaemia

Answer 139

Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by pancytopenia, predisposition to malignancy, and physical abnormalities including short stature, microcephaly, developmental delay, café-au-lait skin lesions, and malformations belonging to the VACTERL-H association. DNA fragility syndrome Pancytopenia Congenital abnormalities at birth (25% will be normal)

Question 140

Diamond Blackfan anaemia

Answer 140

Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that classically presents in infancy. It is characterized by a progressive normochromic, usually macrocytic, anemia; congenital malformations (in approximately 50 percent of patients); and predisposition to cancer. Approximately 90 percent of patients with DBA are diagnosed within the first year of life, with 35 percent diagnosed within the first month. Management Steroids Blood transfusions Iron chelation therapy DDX: TEC - Transient erythroblastopenia of childhood (TEC) is the most common cause of pure red blood cell aplasia in children and should be suspected in an otherwise healthy child with anemia and reticulocytopenia. TEC is a self-limited illness and typically presents between the ages of one and four years.

Question 141

Warm vs cold AIHA

Answer 141

Warm-reactive AIHA – The most common form of primary AIHA in children, accounting for 60 to 90 percent of cases, involves warm-reactive autoantibodies, usually immunoglobulin G (IgG), that bind preferentially to the red cells at 37°C, leading to extravascular hemolysis mainly in the spleen, with resulting anemia, jaundice and, occasionally, splenomegaly. In some cases, IgG is present in sufficient quantity and proximity to fix complement, resulting in features of concomitant intravascular hemolysis. Cold agglutinin disease – Cold agglutinin disease is relatively uncommon in children, amounting to approximately 10 percent of cases, most commonly occurring after Mycoplasma pneumoniae or Epstein-Barr virus infection. In this disorder, immunoglobulin M (IgM) autoantibodies bind erythrocyte I/i or, rarely, anti-PR antigens at colder temperatures and fix complement, which leads to anemia, either due to complement-mediated intravascular hemolysis or immune-mediated extravascular clearance, mainly by hepatic macrophages.

Question 142

NF1 diagnostic criteria

Answer 142

2+ of: 6+ CALMs Axillary/inguinal freckling Optic glioma 2+ Lisch nodules (iris hamartomas) 2+ neurofibromas (or 1+ plexiform neurofibroma) Distinctive osseous lesion (sphenoid dysplasia, tibial pseudoarthrosis) First degree relative with NF1

Question 143

TS criteria

Answer 143

``` MAJOR Hypomelanotic lesion (3+ being >5mm) 3+ angiofibromas 2+ ungual fibromas Shagreen patch Retinal hamartomas Coritcal dysplasias Subependymal nodules Subependymal giant cell astrocytoma Cardiac rhabdomyoma Lymphangioleiomyomatosis 2+ angiomyolipomas ```

Question 144

Zellweger syndrome

Answer 144

``` Peroxisomal disorder AR - PEX1 or 6 most common Prognosis: 6 months Increased VLCFA High forehead, patent fontanelles Severe hypotonia and poor sucking and swallowing Poor subsequent neurological development A/W cerebral gyral abnormalities ```

Question 145

PEX 1 or 6

Answer 145

Zellweger syndrome

Question 146

Cherry-red spot

Answer 146

Tay-Sachs disease (sphingolipidosis - lysosomal storage disorder) Sandhoff disease GM1 gangliosidosis type 1 Niemann-Pick disease (A, C, D) (sphingolipidosis) Sialidosis type 2 Farber disease Mucolipidosis 1

Question 147

Metabolites: VLCFA

Answer 147

Peroxisomal disorders e.g. Zellweger, adrenoleukodystrophy

Question 148

Metabolites: 7-dehydrocholesterol

Answer 148

Smith-Lemli-Opitz syndrome

Question 149

Metabolites: urine glycosaminoglycans and oligosaccharides

Answer 149

Mucopolysaccharidoses and mucolipidoses

Question 150

Metabolites: urinary reducing substances

Answer 150

Galactosaemia

Question 151

Metabolites: urinary AASA

Answer 151

Pyridoxine-dependent seizures

Question 152

PKU

Answer 152

Phenylketonuria - most common IEM in the UK, carrier rate 1 in 50. Untreated: DD in first year of life, learning disability, behavioural problems, decreased pigmentation, dry skin Treated: Asymptomatic Dx: raised phenylalanine, usually NST Rx: Dietary restriction

Question 153

Galactosaemia

Answer 153

Neonatal: jaundice, hepatomegaly, coagulopathy, oil-drop cataracts Later: FTT, proximal tubulopathy, rickets A/W E. coli sepsis Dx: urinary reducing substances, Gal-1-PUT (unless received transfusion, then screen parents) Rx: Lactose-galactose free diet

Question 154

Tay Sachs

Answer 154

2-6 mo old – progressive weakness and loss of motor skills; hypotonia, hyperreflexia, cherry red macula Macrocephaly Seizures, blindness, spasticity Death by 2-5 yo usually; secondary to pneumonia Lysosomal storage disorder / sphingolipidosis Hex A and B

Question 155

Myotonic dystrophy

Answer 155

Neuromuscular condition Severity relates to size of CTG triplet repeat Congenital: unrecognised in mother, preceding polyhydramnios, born unexpectedly flat with facial weakness, hypotonia, respiratory failure, arthrogryposes, joint contractures Older children/adults: facial weakness, progressive weakness, difficulty relaxing muscular contraction, cardiac involvement

Question 156

Lesch Nyhan syndrome

Answer 156

Motor Disorder + Self Mutilation + Hyperuricemia X-Linked Recessive ``` Features Motor: Dystonia, spasticity, choreoathetosis Self mutilating behaviour Gout Intellectual disability ```

Question 157

47 XYY

Answer 157

Jacob's syndrome | Mostly asymptomatic

Question 158

Denys Drash

Answer 158

AD Mutation WT1 transcription factor Triad: Ambiguous genitals, infant onset nephrotic syndrome, Wilms tumour ``` Gonadal dysgenesis, no uterus Diffuse mesangial sclerosis End stage renal failure 0-3 years Wilm’s tumor Mean age of onset = 18 months Gonadoblastoma in some ```

Question 159

Pierson syndrome

Answer 159

Genetics Mutation LAMB2 - B2 laminin ``` Clinical features Nephrotic syndrome (mesangial sclerosis) Hypoplasia ciliary/papillary muscles Fundal pigment abnormalities Strabismus Bilateral fixed narrow pupil Developmental Delay ```

Question 160

Wolff-Chaikoff effect

Answer 160

Wolff-Chaikoff effect is an autoregulatory phenomenon, whereby a large amount of ingested iodine acutely inhibits thyroid hormone synthesis within the follicular cells, irrespective of the serum level of thyroid-stimulating hormone (TSH)

Question 161

SIADH

Answer 161

Criteria: water retention with hypo-osmolality, normal/slightly raised blood volumes, less than maximally dilute urine Causes: - CNS disorder (infection, trauma, hypoxia) - Respiratory illness - Reduced LA filling - Malignancy (lymphoma, bronchogenic carcinoma, idiopathic)

Question 162

Causes obstructive spirometry

Answer 162

Asthma CF Bronchiectasis Obliterative bronchiolitis (often restrictive as well)

Question 163

Causes restrictive spirometry

Answer 163

Chest wall deformity Neuromuscular disease (including GBS) Fibrosing alveolitis Interstitial pneumonitis

Question 164

FEV1

Answer 164

Forced expiratory volume in first second | Gives a measure of large/medium airway obstruction

Question 165

FEF25-75

Answer 165

Forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25-75%) is defined as the mean forced expiratory flow during the middle half of the FVC. Reflects small airway function

Question 166

Total lung capacity

Answer 166

Total volume air in lungs at full inspiration

Question 167

Vital capacity

Answer 167

The total volume of air that can be displaced from the lungs by maximal expiratory effort

Question 168

Residual volume

Answer 168

The volume of air remaining in the lungs after maximum forceful expiration

Question 169

Inspiratory capacity

Answer 169

The maximum volume of air that can be inspired after reaching the end of a normal, quiet expiration. It is the sum of the TIDAL VOLUME and the INSPIRATORY RESERVE VOLUME

Question 170

Functional residual capacity

Answer 170

The volume remaining in the lungs after a normal, passive exhalation Expiratory reserve volume + residual volume

Question 171

Inspiratory reserve volume

Answer 171

It is the amount of air that can be forcibly inhaled after a normal tidal volume

Question 172

Tidal volume

Answer 172

The amount of air that moves in or out of the lungs with each respiratory cycle

Question 173

Expiratory reserve volume

Answer 173

The amount of extra air — above a normal breath — exhaled during a forceful breath out

Question 174

Causes variable intrathoracic obstruction spirometry

Answer 174

This pattern, also known as dynamic or non-fixed intrathoracic obstruction, demonstrates truncation (flattening) of the envelope of the maximal expiratory curve, due to expiratory flow limitation. This pattern may occur with tracheomalacia of the intrathoracic airway, bronchogenic cysts, or with tracheal lesions, which are often malignant. Granulomatous polyangiitis

Question 175

Causes variable extrathoracic obstruction

Answer 175

The flow-volume loop pattern associated with dynamic (non-fixed) extrathoracic obstruction (eg, vocal fold paralysis, extrathoracic tracheomalacia, polychondritis, mobile tumors) is characterized by truncation of the envelope of the maximal inspiratory curve. Vocal cord paralysis Subglottic stenosis Goitre

Question 176

Causes fixed upper airway obstruction

Answer 176

Firm tracheal lesions (eg, tracheal stenosis) can limit the modulating effect of transmural pressures on airway luminal diameter with the result that flow is limited during both inspiration and expiration, causing flattening of both limbs of the flow-volume loop.

Question 177

Leigh disease

Answer 177

``` Subacute necrotising encephalopathy Hypotonia progressive deterioration in neurological abilities Present <2 years: Hypotonia Feeding difficulties Respiratory irregularities Weakness of extraocular movements Ataxia Irritability ```

Question 178

Sturge Weber

Answer 178

Port wine stain, facial naevus, ipsilateral leptomeningeal angioma -> leads to ischaemia, focal seizures, hemiparesis, variable ID. MRI, ophthal*** (glaucoma)

Question 179

Von Hippel Lindau

Answer 179

Tumour suppressor gene Clinical presentation: Cerebellar haemangioblastomas and retinal angiomas Raised ICP Cystic lesions of kidneys, pancreas, liver and epididymis Renal carcinoma (most common form of death) Phaechromocytoma are frequently associated

Question 180

IPEX

Answer 180

FOXP3 Due to decreased number or poor functioning regulatory T cells Clinical features: I – immune dysregulation (dermatitis) P – polyendrocrinopathy (T1DM or thyroiditis) E – enteropathy X – X-linked Consider in: male infant with T1DM + chronic intractable diarrhoea + FTT

Question 181

Ataxia telangiectasia

Answer 181

DNA repair disorder FEATURES Ataxia is earliest manifestation Abnormal eye movements Telangiectasias, can have other skin lesions e.g. CALMS Immune deficiency, affecting both cellular and humoral immunity, occurs in approximately 70 percent of patients ***Progressive lymphopenia +/- antibody deficiency*** Increased risk of leukaemia and lymphoma May have elevated AFP levels (this can help diagnosis)

Question 182

Pompe disease

Answer 182

Glycogen storage disorder 2. Really a lysosomal storage disorder. Accumulation of glycogen in lysosomes. Infantile: Cardiomyopathy and hypotonia. Hypotonia, weakness, hyporeflexia, macroglossia, giant QRS complexes. Enzymology on fibroblasts diagnosis. Elevated CK. Death w/i 12 months (improving with enzyme replacement therapy).

Question 183

Joubert syndrome

Answer 183

Ciliopathy ``` FEATURES Hypotonia Hyperpnoea (disappears by 6mo) Oculomotor apraxia Ataxia Global developmental delay ``` ``` May be associated with Retinal dystrophy Kidney disease Liver disease Polydactyly Hirschprung ``` MRI – molar tooth sign Underdeveloped cerebellar vermis and malformed brain stem

Question 184

Kallman syndrome

Answer 184

Olfactory and GnRH-releasing neurons do not function normally Hypogonadotrophic hypogonadism Hyposmia/anosmia

Question 185

Niemann-Pick Disease

Answer 185

Sphingomyelinoses Splenomegaly + neurological deficit + lipid storage A+B different from C ``` Type A – 1:100 in Ashkenazi Jews - Infantile Hepatosplenomegaly Developmental delay -> death ILD (lung infiltrates) Macular cherry red spots ``` ``` Type B – less severe, later onset - visceral Hepatosplenomegaly Thrombocytopaenia ILD Hyperlipidaemia No neuro involvement ``` Type C Neonate – ascites, abnormal LFT, jaundice (conj bili earliest sign), pulmonary infiltrate, hypotonia Hepatosplenomegaly Neurological deterioration Cherry-red spot Vertical ophthalmoplegia Adults – dementia, depression, BPAD, schizophrenia

Question 186

ODD vs conduct disorder

Answer 186

ODD at least 6 months | Conduct disorder worse and at least 12 months

Question 187

Neonatal atrial flutter

Answer 187

In the newborn with atrial flutter, direct current cardioversion is the usual primary therapy. Adenosine challenge may reveal flutter waves.

Question 188

Mycobacterium avium intracellulare lymphadenitis

Answer 188

Lymphadenitis is the most common manifestation of nontuberculous mycobacterial (NTM) disease in childhood. It typically occurs in children between one and five years of age. The cervicofacial nodes, particularly the submandibular nodes, are most frequently involved. NTM lymphadenitis generally presents as a unilateral, nontender node (<4 cm in diameter) that slowly enlarges over several weeks. The overlying skin then gradually changes from pink to violaceous and thins to become parchment-like and may eventually suppurate through a sinus tract. Fever and other systemic findings are variable and are more common if the lymph nodes become secondarily infected by pyogenic bacteria (eg, staphylococcal or streptococcal species).

Question 189

VSD and AR syndrome

Answer 189

Prolapsed aortic cusp, with resulting AR, is usually associated with outlet VSD and occasionally perimembranous VSD. 5% of VSD patients (higher in Far Eastern countries).

Question 190

Transient antiphopsholipid antibodies

Answer 190

Lupus anticoagulants are acquired inhibitors that may produce a prolonged aPTT. They are commonly seen in children, frequently associated with recent infections, particularly viral infections, and usually are transient. Lupus anticoagulants seen in these clinical settings are neither a risk for bleeding nor for thrombosis.

Question 191

General movement assessment

Answer 191

The General Movements Assessment is a non-invasive and cost-effective tool with demonstrated reliability for identifying infants at risk for cerebral palsy. A normal General Movements Assessment at 3 months in a term high-risk infant is likely associated with a low risk for moderate/severe cerebral palsy. The finding of cramped synchronized General Movements is a strong predictor for the diagnosis of cerebral palsy by 2 years of age in the term population with neonatal encephalopathy. GMA was feasible in an Australian context and accurately identified CP with a sensitivity and specificity comparable with European standards and published neuroimaging data. For detecting CP, we had a sensitivity of 98% and specificity of 94%.

Question 192

Cleidocranial dysostosis/dysplasia

Answer 192

``` Exam stem (2018): 15.You are asked to see an 8-year-old boy with retained deciduous and supernumerary teeth. On further examination you note he has short stature, his fontanelle is still open, and he has hypermobile shoulders as shown. ``` UTD It is characterized by delayed closure of the cranial sutures, distinctive craniofacial features, poor dentition, and hypoplastic clavicles. The skull sutures may take years to close or, in some cases, may never close. Patients with CCD have a broad forehead, midface hypoplasia, and significant dental anomalies that require very close surveillance, including supernumerary teeth, lack of eruption of permanent teeth, and abnormal deciduous dentition.

Question 193

Klippel–Feil syndrome.

Answer 193

Klippel-Feil syndrome is a rare bone disorder distinguished by the abnormal fusion of two or more bones in the neck. Children with the disorder may have a short, webbed neck, decreased range of motion in the head and neck area, and/or a low hairline at the back of the head. Limitation in range of motion of the neck is the most common physical sign. Classic Triad (less than 50%) Limited neck motion Low hairline Short neck

Question 194

Overview of osteogenesis imperfecta features

Answer 194

Clinical manifestations of OI include: ●Excess or atypical fractures (brittle bones) ●Short stature. ●Scoliosis. ●Basilar skull deformities, which may cause nerve compression or other neurologic symptoms. ●Blue sclerae. ●Hearing loss (usually detected in later childhood to early adulthood). ●Opalescent teeth that wear quickly (dentinogenesis imperfecta). ●Increased laxity of the ligaments and skin. ●Wormian bones (small, irregular bones along the cranial sutures). ●Easy bruisability.

Question 195

Facioscapulohumeral dystrophy

Answer 195

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common type of muscular dystrophy. It is a complex genetic disorder characterized in most cases by slowly progressive muscle weakness involving the facial, scapular, upper arm, lower leg, and hip girdle muscles, usually with asymmetric involvement. The age of symptom onset varies from infancy to middle age, but is usually in the second decade.

Question 196

Ehlers Danlos clues

Answer 196

The diagnosis of EDS in one of its forms should be suspected when a patient presents with some combination of features seen in one or several of the types of EDS, including joint hypermobility, multiple joint dislocations, translucent skin, poor wound healing, easy bruising, and unusual scars. This diagnosis should also be considered in any young individual who experiences spontaneous rupture of an organ (eg, gut or uterus) or dissection of a major blood vessel. A variety of clinical features are seen in the different forms of Ehlers-Danlos syndrome (EDS), often resulting in skin hyperextensibility, joint hypermobility, and tissue fragility. Joint dislocations or subluxations are common in most forms of EDS, and joint pain and premature degenerative arthritis are often consequences of the disorder. Pes planus is common in all forms, and pectus excavatum and a high arched palate can also be present in all of the forms of EDS. Musculoskeletal pain is common in patients with joint hypermobility, and complex regional pain syndrome has been described as a rare complication with both the hypermobility and classic forms of EDS.

Question 197

Gram negative diplococci

Answer 197

Neisseria meningitidis, gonorrhoea | Moraxella

Question 198

Gram negative coccobacilli

Answer 198

H. influenzae B. pertussis Pasteurella Brucella

Question 199

Gram negative bacillus

Answer 199

``` E. coli, enterobacter, Klebsiella (EEK) Serratia Pseudomonas Salmonella, Shigella, Yersinia Proteus ```

Question 200

Gram negative comma-shaped

Answer 200

C. jejuni V. cholerae H. pylori

Question 201

Gram positive bacilli

Answer 201

Listeria (aerobic) | Clostridium (anaerobic)

Question 202

Gram positive cocci

Answer 202

Catalase positive = Staph Coagulase positive = S. aureus, negative = CONS (saprophyticus, epidermidis) Catalase negative = Strep Alpha haemolysis: viridans, pneumoniae Beta haemolysis: pyogenes (group A), agalactiae (group B) No haemolysis (gamma?): bovis, Enterococci (group D)

Question 203

Gram positive branching filaments

Answer 203

Nocardia | Actinomyces

Question 204

FRT clinical syndromes - fever alone

Answer 204

Malaria* Typhoid Dengue Hepatitis A *Malaria should be considered in any child with undifferentiated fever up to two years after returning from an endemic region Falciparum malaria is the most common serious infection and cause of death in returning travellers

Question 205

FRT clinical syndrome - fever and diarrhoea

Answer 205

``` Malaria* Typhoid Dengue Hepatitis Travellers’ diarrhoea** Cholera Dysentery (bloody diarrhoea) ``` *Malaria should be considered in any child with undifferentiated fever up to two years after returning from an endemic region **Travellers’ diarrhoea: >3 diarrhoeal episodes in a 24-hour period after travel plus one of the following: cramping, abdominal pain, nausea, vomiting, fever

Question 206

FRT clinical syndromes - fever and respiratory

Answer 206

Malaria* Pneumonia Influenza Tuberculosis (TB) *Malaria should be considered in any child with undifferentiated fever up to two years after returning from an endemic region

Question 207

Dengue

Answer 207

The incubation period of DENV infection ranges from 3 to 14 days; symptoms typically develop between 4 and 7 days after the bite of an infected mosquito. As per RCH lecture, if >14 days cannot be Dengue. ``` Dengue fever — DF (also known as "break-bone fever") is an acute febrile illness defined by the presence of fever and two or more of the following but not meeting the case definition of dengue hemorrhagic fever: ●Headache ●Retro-orbital or ocular pain ●Myalgia and/or bone pain ●Arthralgia ●Rash ●Hemorrhagic manifestations (eg, positive tourniquet test, petechiae, purpura/ecchymosis, epistaxis, gum bleeding, blood in emesis, urine, or stool, or vaginal bleeding) ●Leukopenia ``` Dengue hemorrhagic fever — The cardinal feature of DHF is plasma leakage due to increased vascular permeability as evidenced by hemoconcentration (≥20 percent rise in hematocrit above baseline), pleural effusion, or asciteS. DHF is also characterized by fever, thrombocytopenia, and hemorrhagic manifestations (all of which may also occur in the setting of DF). In the setting of DHF, the presence of intense abdominal pain, persistent vomiting, and marked restlessness or lethargy, especially coinciding with defervescence, should alert the clinician to possible impending DSS (Dengue shock syndrome). Dengue shock syndrome — DSS consists of DHF with marked plasma leakage that leads to circulatory collapse (shock) as evidenced by narrowing pulse pressure or hypotension.

Question 208

FRT clinical syndromes - short incubation <10 days

Answer 208

``` Arboviral infections, eg Dengue, Yellow fever Influenza Campylobacter Shigella Chikungunya ``` Nonspecific (crossing multiple incubation periods in RCH guideline): malaria, typhoid, viral haemorrhagic fever, rickettsial infection

Question 209

FRT clinical syndrome - intermediate incubation (10-21 days)

Answer 209

Measles (median 13 days) Q fever Nonspecific (crossing multiple incubation periods in RCH guideline): malaria, typhoid, viral haemorrhagic fever, rickettsial infection

Question 210

FRT clinical syndromes - long incubation >21 days

Answer 210

``` Hepatitis Rabies Amoebic liver abscess Tuberculosis Filariasis HIV ``` Nonspecific (crossing multiple incubation periods in RCH guideline): malaria, typhoid, viral haemorrhagic fever, rickettsial infection

Question 211

FRT clinical syndromes - acute abdomen of GI haemorrhage

Answer 211

Typhoid (only one listed on RCH guideline)

Question 212

FRT clinical syndromes - jaundice

Answer 212

Viral hepatitis, measles

Question 213

FRT clinical syndromes - fever persisting >2 weeks

Answer 213

Malaria, enteric fever, EBV, CMV, toxoplasmosis, acute HIV, acute schistosomiasis, brucellosis, TB, Q fever

Question 214

FRT clinical syndromes - fever onset >6 weeks after returning

Answer 214

Plasmodium vivax or P ovale, acute hepatitis (B, C or E), TB, amoebic liver abscess

Question 215

Idiopathic intracranial hypertension

Answer 215

Idiopathic intracranial hypertension (IIH) is also called pseudotumor cerebri. It is a disorder defined by clinical criteria that include symptoms and signs isolated to those produced by increased intracranial pressure (eg, headache, papilledema, vision loss), elevated intracranial pressure with normal cerebrospinal fluid (CSF) composition, and no other cause of intracranial hypertension evident on neuroimaging or other evaluations. IIH primarily affects females of childbearing age who are overweight. A typical presentation of IIH is that of an overweight female of childbearing age who complains of headaches and is found to have papilledema on funduscopic examination. Symptoms ●Headache (84 to 92 percent) ●Transient visual obscurations (68 to 72 percent) ●Intracranial noises (pulsatile tinnitus; 52 to 60 percent) ●Photopsia (48 to 54 percent) ●Back pain (53 percent) ●Retrobulbar pain (44 percent) ●Diplopia (18 to 38 percent), typically from nonlocalizing sixth nerve palsy ●Sustained visual loss (26 to 32 percent) ●Neck pain (41 percent) Signs ●Papilledema (hallmark) ●Visual field loss ●Sixth nerve palsy Elevated opening pressure on LP is an essential element of the diagnosis of IIH. The earliest visual field defect in IIH is often an inferior nasal step defect followed by peripheral nasal loss. Arcuate defects may appear next followed by a gradual depression of the entire field, most pronounced peripherally. RCH revision lecture neurologist said diplopia d/t 6th nerve palsy. Rx with acetazolamide

Question 216

NAI - red flag injuries

Answer 216

(RCH) Age dependent Essentially anything in <6mo TEN 4 FACES Clinical Decision Rule (adapted from Pierce et al, 2009) - If these criteria are met, have clinical concern for abuse: Bruising in TEN location (Torso, Ear, Neck) in child <4years-old Any bruising in child <4-6months-old Injury to FACES (Frenulum, Angle of jaw, Cheek, Eyelid, Sclera) in child of any age ``` Any rib fracture Multiple fractures of varying age Skull fractures other than single parietal skull fracture Any other fracture in a non-ambulant child Any long bone fracture EXCEPT - supracondylar humerus - distal radius - mid-clavicular - distal tibial ``` Any suspected or proven intracranial injury except multivehicle collision or high distance fall Any altered conscious state, collapse or arrest. Consider abusive head trauma, ingestion/poisoning, toxins and suffocation Immersion (near drowning in bath or similar) Strangulation or suffocation Female genital mutilation

Question 217

Gastroschisis and omphalocele

Answer 217

Gastroschisis and omphalocele are defects of the abdominal wall that occur in utero, can be detected prenatally using fetal ultrasonography, and result in herniation of abdominal contents. In contrast to omphalocele, there is no sac covering the intestines in gastroschisis. An omphalocele commonly occurs along with other birth defects (such as heart defects and kidney defects) and with specific genetic syndromes (such as Down syndrome, trisomy 18, trisomy 13, and Beckwith-Wiedemann syndrome).

Question 218

NAI concerning fractures

Answer 218

Posteromedial rib fracture. Metaphyseal corner fracture. Key points: All fractures in non-ambulatory children are concerning for abuse. In infants, fractures are more commonly attributed to abuse than to accidents. No specific fracture type is pathognomonic for abuse. Certain locations and types of fractures generate significant concern for an abusive cause (specifically posteromedial rib fractures and metaphyseal corner fractures). Certain skull fractures are concerning for abuse (see VFPMS Guideline: Head injury). Multiple fractures and/or fractures of different ages generate suspicion regarding abuse. Dating of fractures is inexact. Many children with fractures will have minimal or no external sign of injury

Question 219

Cataplexy

Answer 219

Cataplexy is the most specific symptom of narcolepsy. It is seen in approximately 80 percent of children with narcolepsy. It typically emerges around the same time as excessive sleepiness or in the months thereafter. Typical cataplexy is characterized by sudden, transient loss of muscle tone; the weakness or paralysis usually arises in response to strong emotions such as laughter, surprise, anger, fright, or anticipation of reward. Consciousness is fully preserved. Episodes usually last under a minute with full return of function thereafter. The severity of attacks ranges from a slight head or shoulder drop (partial cataplexy) to buckling of the knees and sudden collapse to the floor (full cataplexy). Persistent cataplexy characterized by facial weakness is common in children, manifested by the jaw dropping open, eyelid drooping (ptosis), head rolling, or tongue thrusting movements. This has given rise to the term "cataplectic facies," which is a unique clinical feature of childhood narcolepsy. Excessive daytime sleepiness (EDS) is an essential clinical feature of narcolepsy and is the most common presenting symptom in both children and adults. The classic tetrad of narcolepsy type 1 symptoms is EDS, cataplexy, hypnagogic hallucinations, and sleep paralysis. Hypnagogic hallucinations consist of vivid, dream-like imagery at sleep onset; the same phenomena can more occasionally occur on awakening, when they are then referred to as hypnopompic hallucinations. Sleep paralysis is a momentary inability to move the body, most commonly on awakening in the morning or during the night, but occasionally as one is drifting off to sleep.

Question 220

Oppositional defiant disorder treatment

Answer 220

Parent management training

Question 221

Anorexia nervosa treatment

Answer 221

Family based therapy

Question 222

Syndromes a/w Hirschprung disease

Answer 222

``` Trisomy 21 Bardet Biedl Cartilage hair hypoplasia Congenital central hypoventilation syndrome Familial dysautonomia MEN2 Mowat-Wilson syndrome Smith-Lemli-Opitz Waardenburg syndrome ```

Question 223

Premature adrenarche

Answer 223

Adrenarche refers to the progressive maturation of the adrenal cortex that normally becomes manifest after five years of age and is associated with an increased serum dehydroepiandrosterone sulfate (DHEAS) level. Pubarche is the physical manifestation of adrenarche and is characterized by the development of pubic hair, axillary hair, adult apocrine body odor, acne, and increased oiliness of hair and skin. Pubarche is considered premature if it develops before age eight years in girls and nine years in boys. Premature adrenarche, indicated by a premature elevation of DHEAS levels, is the most common cause of premature pubarche. Premature adrenarche is considered to be a variant of normal development. It is a diagnosis of exclusion. If no other evidence secondary sexual characteristics, normal linear growth velocity, no history exogenous androgen exposure, and normal bone age, nil further required. Otherwise check DHEAS, 17OH, androstenedione and testosterone. Raised DHEAS but normal/<200 17OH still consistent with premature adrenarche. As per UTD, puberty often starts 1-2 years earlier than average for these kids, and as per a paper, final height is normal.

Question 224

Loeys-Dietz syndrome (LDS)

Answer 224

Gene: TGFBR1/2 Similar to Marfans: Aortic aneurysm/dissection Differences: Bifid uvula/cleft palate, arterial tortuosity, hypertelorism, diffuse aortic and arterial aneurysms, craniosynostosis, clubfoot, cervical spine instability, thin and velvety skin, easy bruising. Most patients with a TGFBR1 or TGFBR2 mutation have Loeys-Dietz syndrome, which is often characterized by hypertelorism (widely spaced eyes), a split uvula or cleft palate, tortuous arteries, and aortic aneurysms.

Question 225

Time of onset food poisoning

Answer 225

Hours - Staph, Bacillus cereus 24hrs-days - E. coli, Salmonella, Campylobacter, Shigella 7 days - Protozoans e.g. Crytosporidium For suspected foodborne, illness, the timing of symptom onset following exposure to the suspect food can be informative. Ingested preformed toxins (eg, those produced by Staphylococcus aureus and Bacillus cereus) cause illness within hours of exposure, whereas ingested pathogens that subsequently produce toxin (eg, enterotoxigenic Escherichia coli) or directly damage or invade across the intestinal epithelial cell wall (eg, Salmonella, Campylobacter, Shigella) usually result in symptoms after approximately 24 hours or longer. Protozoal pathogens (eg, Cryptosporidium parvum) generally produce enteric illness after an incubation period of approximately seven days.

Question 226

Juvenile myelomonocytic leukaemia

Answer 226

Associated with NF1 and Noonan syndrome The vast majority of children with JMML have somatic and/or germline mutations of genes involved in the RAS/MAPK signaling pathway. A group of distinctive genetic syndromes arise from germline mutations in genes of the RAS/MAPK pathways. These mutations induce constitutive activation of the pathway, and are collectively known as "RASopathies," or neuro-cardio-facio cutaneous syndromes.

Question 227

Bronchiolitis obliterans

Answer 227

Adenovirus Bronchiolitis obliterans describes a pattern of histologic abnormalities affecting the small airways, characterized by large-airway bronchiectasis and fibroproliferative thickening of the bronchiolar walls that narrows the bronchiolar lumen and may progress to the complete obliteration of bronchioles. In children, the most common cause is postinfection (postinfectious bronchiolitis obliterans), which has been particularly described after adenovirus and, less commonly, with mycoplasma pneumonia.

Question 228

Fluid intake goals prevention nephrolithiasis

Answer 228

In all children with nephrolithiasis, adequate fluid intake is a key component to reducing the risk of recurrent stones. High fluid intake increases the urine flow rate and lowers the urine solute concentration, thereby reducing the likelihood of new stone formation. Fluid intake is targeted to maintain the following 24-hour urine volumes based upon age: ●Infants – ≥750 mL ●Small children below five years of age – ≥1000 mL ●Children between 5 and 10 years of age – ≥1500 mL ●Children greater than 10 years of age – ≥2000 mL

Question 229

Rasopathies

Answer 229

Noonan ,NF1, Costello, cardiofacialcutaneous syndrome

Question 230

Aurer rod

Answer 230

AML

Question 231

Reed Sternberg cell

Answer 231

Hodgkin lymphoma | EBV

Question 232

Th1 phenotype

Answer 232

IFN gamma Macrophages IgG

Question 233

Th2 phenotype

Answer 233

IL4/5/13 Mast cells, eosinophils IgE

Question 234

Th17 phenotype

Answer 234

IL 17, 22 | Neutrophils, monocytes

Question 235

6 week milestones

Answer 235

Head lag Fix and follow 90 degrees Smile

Question 236

3 month milestones

Answer 236

Raise head prone, no head lage F+F 180 degrees, hand to midline Vowel sounds, turn to sound

Question 237

6 month milestones

Answer 237

Roll, sit with support Transfer, reaches, mouthing Babble, turns to name Play with feet, holds bottle when feed

Question 238

9 month milestones

Answer 238

Sit without support, stand with support 2 syllable bable Finger feeds

Question 239

12 month milestones

Answer 239

Crawl, pull to stand Pincer grip 2 words with meaning Wave, clap

Question 240

15 month milestones

Answer 240

Walks well Several words, echolalia Drink from cup, points with purpose

Question 241

18 month milestones

Answer 241

Scribble 50 words, 1 step commands Spoon, takes shoes/socks off

Question 242

2 year milestones

Answer 242

Climb stairs one at a time, kick ball Vertical line, 8 block tower 2 step command Plays alone, spoon and fork

Question 243

3 year milestones

Answer 243

Tricycle, jump Circle 3-4 words sentence Less stranger danger, knife and fork, dress self

Question 244

4 year milestones

Answer 244

Hops Cross and square, man with 3 parts Count to 10 Brush teeth

Question 245

5 year milestones

Answer 245

Climbs stairs one foot per step Triangle, 6 part man, buttons Role play

Question 246

Azathioprine metabolism

Answer 246

AZA -> 6MP 6MP -> 6TU, 6MMP, 6TGN ``` 6TU = inactive, urine excretion 6MMP = inactive, hepatotoxic 6TGN = active, myelosuppression ``` TPMT metabolises to 6TU and 6MMP Allopurinol increases ratio of 6TGM to 6MMP, therefore increasing myelosuppression and reducing hepatotoxicity Xanthine oxidase metabolises 6MP to 6TU

Question 247

Heliotrope rash

Answer 247

Dermatomyositis Bilateral lilac discolouration of the eyelids (particularly the upper eyelids) with swelling of the eyelids and skin around the eyes.

Question 248

Dermatitis herpetiformis

Answer 248

Dermatitis herpetiformis is a rare but persistent immunobullous disease that has been linked to coeliac disease. The name herpetiformis is derived from the tendency for blisters to appear in clusters, resembling herpes simplex. However, dermatitis herpetiformis is not due to viral infection. Mean age 7. Buttocks, elbows, knees, back of neck, scalp. Itchy.

Question 249

Congenital hepatic fibrosis

Answer 249

ARPKD - invariably associated with CHF

Question 250

Atomoxetine side effects

Answer 250

Increased suicidal ideation | Cardiotoxicity

Question 251

Information bias

Answer 251

Information bias is any systematic difference from the truth that arises in the collection, recall, recording and handling of information in a study, including how missing data is dealt with.

Question 252

Russel Silver genes

Answer 252

Chromosome 11 or 7 | Loss of paternal genes

Question 253

ROHHAD

Answer 253

Rapid-onset Obesity, Hypothalamic dysfunction, Hypoventilation, Autonomic Dysregulation Syndrome *Rapid weight gain in childhood (over 6-12months) – usually first feature Followed by endocrine abnormalities (Cushings, *GH def., precious puberty, hypothyroidism) Autonomic dysreg eg temperature instability *Central hypoventilation syndrome may increase over time Cardiorespiratory arrest* +/- Seizures, Dev delay/behavioural issues At risk of neural crest tumours: ganglioneuroma/neuroblastoma

Question 254

Langerhans cell histiocytosis

Answer 254

Monocyte lineage Bone lesions (osteolytic, skull) Skin lesions (refractory dermatitis) Can have hypothalamic involvement e.g. central DI, poor growth

Question 255

Pendred syndrome

Answer 255

AR defect pendrin protein = anion exchanger SNHL + goitre Dyshormonogenesis, subclinical hypothyroidism

Question 256

Superior axis

Answer 256

``` AVSD TA Noonans LTGA ALCAPA ```

Question 257

Vitamin A deficiency

Answer 257

Xerophthalmia - night blindness, dry eyes

Question 258

Vit D def

Answer 258

Low Ca Low PO4 Rickets

Question 259

Vit E def

Answer 259

Neuropathy, ataxia, retinal degeneration, haemolytic anaemia

Question 260

Vit K def

Answer 260

Bleeding (2, 7, 9, 10), raised INR/APTT

Question 261

Folate deficiency

Answer 261

Hypersegmented neutrophils, megloblastosis, anaemia A/W low zinc and B12 Raised homocysteine

Question 262

B1 def

Answer 262

Thiamine Beriberi Cardiomyopathy and polyneuritis

Question 263

Vitamin A deficiency

Answer 263

Xerophthalmia - night blindness, dry eyes

Question 264

Vit D def

Answer 264

Low Ca Low PO4 Rickets

Question 265

B12 def

Answer 265

Megaloblastic anaemia, atrophic glossitis, neuropathy/demyelination Raised methylmalonic acid

Question 266

Vit K def

Answer 266

Bleeding (2, 7, 9, 10), raised INR/APTT

Question 267

Folate deficiency

Answer 267

Hypersegmented neutrophils, megloblastosis, anaemia | A/W low zinc and B12

Question 268

B1 def

Answer 268

Thiamine Beriberi Cardiomyopathy and polyneuritis

Question 269

B2 def

Answer 269

Riboflavin | Angular stomatitis, glossitis, seborrheic dermatitis, corneal vascularisation

Question 270

B3 def

Answer 270

Niacin | Pellagra -> dermatitis, diarrhoea, dementia, weakness

Question 271

B12 def

Answer 271

Megaloblastic anaemia, atrophic glossitis, neuropathy/demyelination Raised methylmalonic acid

Question 272

Vit C def

Answer 272

Ascorbic acid | Scurvy -> haemorrhage (gums), follicular hyperkeratosis, haemolytic anaemia

Question 273

Hypocalcaemia - signs

Answer 273

Tetany, seizures, Chvostek/Trousseau signs

Question 274

Hypophosphataemia - signs

Answer 274

Myopathy, rhabdomyolysis, osteomalacia/rickets

Question 275

Hypomagnesaemia - sign

Answer 275

A/W hypokalaemia (renal potassium wasting)/hypocalcaemia | Fasciculations, tremors, spasm, personality changes, seizures

Question 276

Iron deficiency

Answer 276

Most common deficiency Microcytic hypochromic anaemia Pagophagia is specific Cardiomegaly

Question 277

HBIG

Answer 277

Neonates of mothers who are surface antigen positive

Question 278

Copper deficiency

Answer 278

Sideroblastic anaemia (nucleated red cells), neurtopenia, FTT, osteoporosis

Question 279

Selenium deficiency

Answer 279

Cardiomyopathy (dilated) -> Keshan disease

Question 280

Iodine deficiency

Answer 280

Goitre, hypothyroidism, cretinism (Id, hearing impairment, spastic diplegia, strabismus)

Question 281

VZV infectious periods

Answer 281

2 days prior to rash, until all lesions crusted

Question 282

ZIG indications

Answer 282

Susceptible pregnant women, neonates whose mother develop VZV -7 to +2 days either side of delivery, neonates <30 days if mother no history of infection or neg serology, neonates <28/40.

Question 283

HBIG

Answer 283

Neonates of mothers who are surfance antigen positive

Question 284

Highest risk needle stick injury virus

Answer 284

HBV | Then HCV, then HIV

Question 285

PIMS TS criteria/details

Answer 285

PIMS-TS should be considered in an unwell child who presents with fever (≥3 days), signs of shock, rash and abdominal pain. Critera: - Fever, inflammation (neutrophilia, CRP, lymphopenia), organ dysfunction (shock, cardiac, resp, GI, neuro), "additional features" - Exclusion of bacterial sepsis, staph/strep shock syndromes, infections a/w myocarditis (e.g. enterovirus) - COVID 2-6 weeks prior Generally older cf KD (11 vs 2 yrs) More GI symptoms Higher rates myocarditis and aKI

Question 286

Obesity - syndromic, DD

Answer 286

PWS | Albright hereditary osteodystrophy (?pseudohypoparathyroidism), Bardet-Biedl

Question 287

Grey baby syndrome

Answer 287

Chloramphenicol during 3rd trimester | Cyanosis, abdo distension, vasomotor collapse, death

Question 288

Imprinting - PWS/Angelman

Answer 288

Chromosome 15 PWS - paternal = absent paternal expression, or both maternal Angelman - maternal = absence of maternally functioning genes

Question 289

Imprinting - BWS/RSS

Answer 289

``` Chromosome 11 (also 7 for RSS) Paternally expressed growth factors -> BWS = two paternal, RSS = two maternal (or absence etc) ```

Question 290

Imprinting pedigree e.g. maternal imprinting

Answer 290

No children of an affected female are affected | Half the children of an affected male or male with mutation will be affected

Question 291

Septo-optic dysplasia

Answer 291

``` Clinical diagnosis 2+: - optic nerve hypoplasia - pituitary hormone abnormalitieis - midline brain defects, including agenesis of corpus callosum and/or septum pellucidum ``` Early forebrain maldevelopment Variable phenotype Aetiology unclear

Question 292

Red man syndrome

Answer 292

Vancomycin infusion reaction Parenteral administration (bioavailability <10%) Flushing, erythema, pruritis. Rarely life threatening. DT direct activation of mast cells DDX anaphylaxis

Question 293

Grey baby syndrome

Answer 293

Chloramphenicol during 3rd trimester | Cyanosis, abdo distension, vasomotor collapse, death

Question 294

Friedreich ataxia

Answer 294

Most common hereditary ataxia, carrier frequency 1 in 85 Features - onset 10-15yo - progressive ataxia, absent LL reflexes, extensor plantars, reduced vibration/proprioception - deformities e.g. scoliosis, foot deformities - cardiomyopathy - diabetes FXN -> frataxin - involved in iron sulphur cluster synthesis, relates to respiratory chain proteins - deficiency = susceptibility to oxidative stress - 96% due to GAA (‘Genetic AtaxiA’) repeat expansion in intron 1 of FXN

Question 295

UCD not causing hyperammonemia

Answer 295

Arginase deficiency

Question 296

UCD typical presentation

Answer 296

Severe defects typically present in term newborns who appear well for the first 24 to 48 hours after birth. The infant becomes symptomatic after feeding has started because human milk or infant formula provides a protein load. Initial signs include somnolence, inability to maintain normal body temperature, and poor feeding, usually followed by vomiting, lethargy, and coma, a presentation that is identical to that of an infant with sepsis. However, the absence of risk factors for sepsis and a nondiagnostic sepsis evaluation should prompt consideration of a metabolic disorder. A common early sign in newborns with hyperammonemia is central hyperventilation leading to respiratory alkalosis.

Question 297

Hyperammonemia ddx

Answer 297

UCD Organic acidaemias Fatty acid oxidation defect Disorders pyruvate metabolism Acidosis -> organic acidaemia, pyruvate metabolism Normal pH/alkalosis, hypoglycaemia and hypoketonemia -> fatty acid oxidation defect

Question 298

Biliary cyst

Answer 298

The majority of patients with biliary cysts will present before the age of 10 years. The classic presentation includes the triad of abdominal pain, jaundice, and a palpable mass, and is more common in children than adults. Infants typically present with obstructive jaundice and abdominal masses, children more often present with abdominal pain and nausea/vomiting. Biliary cysts must be differentiated from cystic biliary atresia. In infants with biliary cysts, the intrahepatic bile ducts are normal or dilated rather than sclerosed.

Question 299

Glycogen storage disease

Answer 299

Liver, muscles, kidneys. Inability to break down glycogen. Hepatic forms = hepatomegaly and hypoglycaemia. Muscle forms = weakness and fatigue. Massive hepatomegaly in the absence of splenomegaly (glycogen not stored in spleen, helps differentiate from lysosomal storage disorders). Abnormal fat distrubtion. FTT. Bruising. Nephromegaly. Hypoglycaemia. Raised lactate. Hyperuricaemia. Hyperlipidaemia.

Question 300

Facial features fetal alcohol syndrome

Answer 300

Short palpebral fissure, thin vermillion border, smooth philtrum. Clinical findings in a newborn with FAS include a characteristic pattern of facial anomalies, with short palpebral fissures, a thin upper lip, and a long, smooth philtrum. Pre and postnatal growth retardation, neonatal irritability, microcephaly, learning disability, hyperactivity in childhood, cardiac defects (VSD, ASD), small nails on fifth fingers/toes, facial anomalies. ``` Small Dysmorphic Microcephaly, ID CHD Postnatal growth failure ```

Question 301

Which antiepileptic is associated with the highest risk of congenital malformation?

Answer 301

Google: Among the AEDs, valproate was associated with the highest risk of malformation (10.93%; 95% CI, 8.91-13.13).

Question 302

Shockable rhythm - voltage

Answer 302

4J/kg DC shock, asynchronous | Adult "dose" - biphasic defib 120-200J, monophasic up to 360J.

Question 303

Thrombin time

Answer 303

The thrombin time (TT) measures the final step of coagulation, the conversion of fibrinogen to fibrin. The thrombin time is prolonged if fibrinogen levels are low or if an anticoagulant that inhibits thrombin is present in the sample.

Question 304

Detecting heparin in coags

Answer 304

If heparin is present, the TT will be significantly prolonged and the reptilase time will be normal. eparin is an indirect thrombin inhibitor that complexes with antithrombin (AT), converting AT from a slow to a rapid inactivator of thrombin (factor IIa), factor Xa, and, to a lesser extent, factors IXa, XIa, and XIIa. The reptilase time (RT) is similar to the TT in measuring the conversion of fibrinogen to fibrin [26]. However, unlike the TT and the aPTT, the RT is insensitive to the effects of heparin because reptilase, an enzyme derived from the venom of Bothrops snakes, is not inhibited by antithrombin or the antithrombin-heparin complex.

Question 305

Kingella kingae

Answer 305

K. kingae, a gram-negative organism present in oral microbiome, is being increasingly identified as a cause of osteomyelitis in children 6 to 36 months of age, and some reports suggest K. kingae is the most common cause of osteomyelitis in Switzerland and France. It may rarely cause osteomyelitis in older children. K. kingae often affects nontubular bones (eg, sternum, vertebrae, calcaneum) and generally produces milder symptoms than osteomyelitis caused by gram-positive pathogens. K. kingae is a fastidious organism that is difficult to isolate by conventional culture techniques. Inoculation of specimens into blood culture vials and, especially, molecular diagnostic methods (eg, polymerase chain reaction amplification) may increase detection. K. kingae osteomyelitis generally affects children between 6 and 36 months of age and is typically milder and more indolent than osteomyelitis due to other pathogens. In one series of 43 children with K. kingae osteoarticular infections, only 15 percent of children were febrile at presentation, and 39 percent had normal inflammatory markers. K. kingae may disproportionately affect nontubular bones (eg, sternum, vertebrae, calcaneum).

Question 306

Osteomyelitis organisms/features

Answer 306

GRAM POSITIVE Staphylococcus aureus: All ages; possible associated skin or soft tissue infection; MRSA may be associated with venous thromboembolism and pulmonary disease. Coagulase-negative staphylococci: Neonates in intensive care unit; children with indwelling vascular catheters (eg, for chronic hemodialysis). Group B Streptococcus: Infants younger than 3 months (usually 2 to 4 weeks). Streptococcus pneumoniae: Children younger than 2 years who are incompletely immunized; children older than 2 years with underlying medical conditions (eg, sickle cell disease, asplenia, splenic dysfunction, immunodeficiency, chronic heart disease, chronic lung disease, diabetes mellitus). GRAM NEGATIVE Kingella kingae: Children 6 to 36 months; indolent onset; oral ulcers preceding musculoskeletal findings; may affect nontubular bones. Nonsalmonella gram-negative bacilli (eg, Escherichia coli, Serratia): Birth to 3 months; children with sickle cell disease; instrumentation of the gastrointestinal or urinary tract; immunocompromised host (eg, CGD). Salmonella species: Children with sickle cell disease or related hemoglobinopathies; exposure to reptiles or amphibians; children with gastrointestinal symptoms; children in resource-limited countries.

Question 307

Iron deficiency iron studies

Answer 307

Transferrin and TIBC up, everything else down.

Question 308

Degeneration of grey matter metabolic disorders

Answer 308

``` Tay Sachs Gaucher Niemann Pick Batten Leigh Menkes ```

Question 309

Degeneration of cerebral white matter metabolic disorders

Answer 309

Krabbe Metachromatic leukodystrophy Canavan disease

Question 310

Metachromatic leukodystrophy

Answer 310

A rare autosomal recessive lysosomal storage disease that causes progressive demyelination of the central and peripheral nervous system. Three major subtypes of MLD are primarily distinguished by the age at disease onset: ●Late infantile onset (age 6 months to 2 years) ●Juvenile onset (age 3 to <16 years) ●Adult onset (age ≥16) Peripheral neuropathy occurs in all forms and may be a presenting feature, particularly in the late infantile form. The late infantile form of MLD typically appears at six months to two years of age. Infants and toddlers may present with developmental delay or regression of motor skills due to the peripheral nerve involvement even before any evidence of brain magnetic resonance imaging (MRI) changes. Other early signs can include gait difficulties, seizures, ataxia, hypotonia, extensor plantar responses, and optic atrophy. Deep tendon reflexes are sometimes reduced or absent, reflecting the peripheral neuropathy. Brain MRI reveals symmetric white matter lesions with a periventricular and/or frontal predominance.

Question 311

Krabbe disease

Answer 311

Most patients with Krabbe disease present with symptoms within the first twelve months of life. A peripheral motor-sensory neuropathy occurs in most patients. Symptoms usually develop from ages two to twelve months with infantile onset Krabbe disease. Manifestations include irritability, feeding difficulty, reflux, developmental delay, limb spasticity, axial hypotonia, optic atrophy, and decreased growth. Deep tendon reflexes may be increased early when spasticity predominates but diminish and are lost as neuropathy worsens. Irritability is the most common initial symptom. In late infantile onset Krabbe disease, patients present between 13 months and 36 months. Initial symptoms include abnormal gait, irritability, slurred speech, or vision difficulties. Clinical indicators include appendicular hypertonia, axial hypotonia, abnormal protective reflexes, abnormal deep tendon reflexes, constipation, and abnormal pupillary response. Visual difficulty, apneic episodes, seizures, and temperature instability are more likely as the disease progresses. The median age of death is six years. In children with infantile-onset Krabbe disease, the most frequent MRI abnormalities involve the deep cerebral white matter, dentate nucleus, and cerebellar white matter.

Question 312

Approach to metabolics - failure to make/break complex molecules

Answer 312

Dysmorphic syndromes at birth d/t abence of structural molecules important for embryogenesis. Smith-Lemli-Opitz - cholesterol synthesis defect Zellweger syndrome - peroxisomal Congenital disorders of glycosylation / glycosylation defects Many appear normal at birth and become progressively more obvious with time.

Question 313

Approach to metabolics - intoxication

Answer 313

Symptom free period before decompensation with toxic metabolite build up, e.g. once feeds established in neonates. Classically collapse day 3 of life. DDX sepsis, duct dependent cardiac problem. Aminoacidopathies - tyrosinaemia, MSUD UCD Organic acidaemias Sugar intolerances - galactosaemia

Question 314

Approach to metabolics - energy insufficiency

Answer 314

Immediate onset symptoms in congenital lactic acidosis: - respiratory chain defects (?mitochondrial) - pyruvate metabolism defects Presentation only when delay in fuel provision (may not present for months): - fat oxidation defects e.g. medium chain acyl-CoA dehydrogenase - glycogen storage disease - defects in gluconeogenesis e.g. fructose bisphophaatse deficiency

Question 315

Hypoketotic hypoglycaemia ddx

Answer 315

Hyperinsulinism Fat oxidation defect Liver failure Mitochondrial disorder

Question 316

Raised serum urate ddx

Answer 316

End product of purine breakdown. Lesch-Nyhan syndrome (X linked disorder purine metabolism) GSD type 1 Rhabdomyolysis Familial juvenile hyperuicaemic nephropathy

Question 317

Neonatal chlamydia conjunctivitis

Answer 317

The most frequent clinical manifestation of C. trachomatis infection in the newborn is conjunctivitis. The incubation period for C. trachomatis conjunctivitis is 5 to 14 days after delivery. Presentation before five days is unusual. Clinical findings of conjunctivitis range from mild swelling with a watery eye discharge, which becomes mucopurulent, to marked swelling of the eyelids with red and thickened conjunctivae (chemosis). A pseudomembrane may form as the exudate adheres to conjunctiva. The conjunctivae may also be very friable, resulting in bloody discharge. Among infants born to mothers with cervical C. trachomatis infection, 5 to 30 percent develop pneumonia. Approximately one-half of these infants have a history of conjunctivitis. Pneumonia due to C. trachomatis is recognized in most affected infants between 4 and 12 weeks of age, although essentially all are symptomatic before eight weeks. Cough and nasal congestion without significant discharge are common. Oral azithromycin is the preferred treatment for neonatal C. trachomatis infections, including both conjunctivitis and pneumonia. Erythromycin base, 50 mg/kg/day in four divided doses for 14 days, is an alternative. Gram negative.

Question 318

GLUT 1 deficiency syndrome

Answer 318

A low CSF glucose in a child with no symptoms of infection and an otherwise normal CSF profile often is ignored, but may be the critical laboratory finding in the diagnosis of a rare disorder called glucose transporter protein syndrome (GLUT1 deficiency syndrome), which has a deficiency of the enzyme necessary for the transport of glucose into the CSF. Diagnosis can be confirmed by an erythrocyte glucose uptake assay that shows low uptake. Molecular genetic testing for pathogenic variants in SLC2A1 can also be used to identify some of these patients. Infants with this disorder have slowly progressive neurologic deterioration, seizures (often absence-type), and occasionally microcephaly. Although few cases have been reported, it is probably underdetected. Glucose load may bring about transient improvement. Children with this disorder are treated with the ketogenic diet.

Question 319

Myoclonic epilepsy with red-ragged fibres

Answer 319

Myoclonic epilepsy with ragged red fibers (MERRF) is characterized by myoclonus, typically as the first symptom, and is associated with generalized epilepsy, ataxia, and myopathy. Additional features can include dementia, optic atrophy, bilateral deafness, peripheral neuropathy, spasticity, lipomatosis, and/or cardiomyopathy with Wolff-Parkinson-White syndrome. Childhood onset after a normal early development is common. MERRF is caused by mutations in mitochondrial DNA. More than 80 percent of patients suffering from MERRF harbor an A to G mutation at nucleotide 8344 in the mitochondrial MT-TK gene encoding tRNA(Lys).

Question 320

Conduct disorder is a known precursor to which personality disorder?

Answer 320

Antisocial personality disorder

Question 321

Urticarial vasculitis

Answer 321

Urticarial vasculitis should be considered when the hives are painful rather than pruritic, last longer than 48 hours, leave residual bruising or pigmentation changes, or recur whenever glucocorticoids are tapered. Patients with urticarial vasculitis may also report fever, chills, and arthralgias. Urticarial vasculitis may occur in isolation or in patients previously diagnosed with other systemic inflammatory diseases, such as Sjögren syndrome or systemic lupus erythematosus. Skin biopsy is indicated if signs or symptoms of vasculitis are present.

Question 322

Dermatographism

Answer 322

Patients with this condition develop the rapid onset of a wheal-and-flare reaction after firm stroking, scratching, or the application of pressure to the skin. Dermographism is the most common of the inducible urticarias and is often an incidental finding in the evaluation of other skin conditions, most commonly atopic dermatitis, chronic spontaneous urticaria, and the other inducible urticarias discussed in this topic. In simple dermographism, a wheal is provoked by stroking, scratching, or rubbing the skin. The wheal typically appears within 6 to 7 minutes and begins to fade 15 to 30 minutes later.

Question 323

Which feature best differentiates urticarial vasculitis from chronic idiopathic urticaria?

Answer 323

Persistence of individual lesions Urticarial vasculitis is also hypocomplementaemic, while normal urticaria has normal levels of complement.

Question 324

You are requested to urgently review a 15-year-old boy with autism spectrum disorder presenting with acute onset torticollis. He has recently commenced risperidone 2 mg for behavioural disturbance. What is the most appropriate treatment for his torticollis? A. Benztropine. B. Ibuprofen. C. Lorazepam. D. Olanzapine. E. Promethazine.

Answer 324

Acute dystonic reaction. AMH: Dystonias: Torticollis, carpopedal spasm, trismus, perioral spasm and oculogyric crisis, as well as medical emergencies, such as laryngeal spasm and opisthotonos, may occur. Dystonias are more common in children and young adults, and more likely with high doses. They often occur within 24–48 hours of starting treatment or increasing dose, and respond rapidly to anticholinergics such as benzatropine. In some cases treatment with a benzodiazepine may also help. It may be possible to reintroduce the drug at a lower dose, or consider an alternative.

Question 325

Angelman syndrome testing

Answer 325

If AS is suspected, the workup should include methylation studies first, followed by chromosome microarray

Question 326

Multiple focal liver or spleen lesions on imaging for persistent fever

Answer 326

Suspect candida Clinical suspicion — Although many children with invasive candidiasis have no obvious clinical manifestations, we suspect candidemia or invasive candidiasis in children with risk factors who have: ●Unexplained fever or signs of severe sepsis while receiving adequate antibiotics ●Skin lesions suggestive of invasive candidiasis (eg, multiple, nontender, erythematous, pustular or nodular lesions ●Eye findings suggestive of invasive candidiasis ●Multiple focal liver or spleen lesions on imaging for persistent fever

Question 327

Antibiotic choice (oral) for presumed MRSA cellulitis/abscess - exam stem is 3yo with cellulitis/abscess not responding to cephalexin.

Answer 327

TMP/SMX. ETG: For patients at increased risk of community-associated MRSA, use trimethoprim+sulfamethoxazole or clindamycin. UTD: Isolates resistant to oxacillin or methicillin are resistant to other beta-lactam agents, including cephalosporins (with the exception of ceftaroline and ceftobiprole). Definitive therapy for invasive methicillin-resistant S. aureus (MRSA) infections depends upon the type of infection, susceptibility of the isolate, and results of testing for inducible resistance to clindamycin. At home — Treatment of MRSA at home usually includes a 7- to 10-day course of an antibiotic (by mouth) such as trimethoprim-sulfamethoxazole (brand name: Bactrim), clindamycin, minocycline, linezolid, or doxycycline. Fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin) and macrolides (e.g., erythromycin, clarithromycin, azithromycin) are NOT recommended for treatment of MRSA because of ready development of resistance.

Question 328

Examples mitochondrial inheritance disorders

Answer 328

Mitochondrial myopathy Diabetes mellitus and deafness (DAD) Leber's hereditary optic neuropathy (LHON)***prev Q - visual loss beginning in young adulthood Leigh syndrome, subacute sclerosing encephalopathy - after normal development the disease usually begins late in the first year of life, although onset may occur in adulthood - a rapid decline in function occurs and is marked by seizures, altered states of consciousness, dementia, ventilatory failure Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP) Myoneurogenic gastrointestinal encephalopathy (MNGIE) MERRF syndrome MELAS syndrome Mitochondrial DNA depletion syndrome

Question 329

Treatment hereditary angioedema

Answer 329

In HAE, deficiency or dysfunction of C1 inhibitor (C1-INH) leads to excessive production of the vasoactive mediator bradykinin, which leads to episodic increases in vascular permeability and angioedema. The bradykinin-mediated angioedema of HAE is fundamentally different from the angioedema that occurs with allergic reactions (which is mediated by histamine and other mast cell mediators), and it does not respond to epinephrine, antihistamines, or glucocorticoids. Instead, first-line therapies for HAE act by replacing C1-INH or by blocking the production or function of bradykinin. Treatment: C1 inhibitor Bradykinin B2-receptor antagonist — Icatibant Ineffective: - Adrenaline (bradykinin mediated, no histamine mediated) - Steroids

Question 330

Pulmonary haemosiderosis triad

Answer 330

Hemoptysis, iron deficiency anemia and diffuse pulmonary infiltrates

Question 331

Chikungunya

Answer 331

West Africa Chikungunya virus is an arthropod-borne alphavirus transmitted by mosquitoes that causes acute febrile polyarthralgia and inflammatory arthritis as well as acute cutaneous eruptions and other systemic manifestations.

Question 332

Leptospirosis

Answer 332

Leptospirosis is a zoonosis with protean clinical manifestations caused by pathogenic spirochetes of the genus Leptospira. Various mammals are natural hosts; humans are infected incidentally after animal or environmental exposure. The clinical course of leptospirosis is variable. Most cases are mild and self-limited or subclinical, while some are severe and potentially fatal. The illness generally presents with the abrupt onset of fever, rigors, myalgias, and headache in 75 to 100 percent of patients, following an incubation period of 2 to 26 days (average 10 days). Conjunctival suffusion, characterized by conjunctival redness, is an important but frequently overlooked sign

Question 333

Typhoid/enteric fever

Answer 333

Enteric fever is characterized by severe systemic illness with fever and abdominal pain. Caused by Salmonella enterica (various subtypes). Enteric fever is a febrile illness with onset of symptoms 5 to 21 days after ingestion of the causative microorganism in contaminated food or water. Classic presentation: - week 1: rising, stepwise fever and bacteraemia, chills, relative bradycardia or pulse-temperature dissociation - week 2: abdominal pain, rose spots (faint salmon-coloured macules) on trunk and abdomen - week 3: HSM, GI bleeding, perforation d/t ileocecal lymphatic hyperplasia of Peyers patches - septic shock may develop. In the absence of acute complications or death from overwhelming sepsis, symptoms gradually resolve over weeks to months.

Question 334

Diffuse intrinsic pontine glioma

Answer 334

The clinical course for children with DIPG is rapid. Most symptoms start less than four weeks before seeking medical attention. Symptoms are caused by dysfunction of pontine structures, including long tracts and cranial nerve nuclei. Diplopia is usually the first sign secondary to abducens nerve palsy. Damage to the facial nucleus will produce facial weakness or paralysis. Damage to the long motor tracts will produce weakness and hyperreflexia. Dysfunction of the cerebellopontine connections will cause ataxia, dysmetria, dysarthria. A classic triad in DIPG is present in about 50% of the patients, which includes long tract signs, cerebellar signs, and cranial nerve neuropathies. Hydrocephalus occurs in less than 10% of the cases. Account for approximately 80% of pediatric brainstem tumors and with male to female ratio as 1:1. It is more common in younger age group. These tumors are almost always highly malignant and fatal. The most common symptoms are cranial nerve palsies, most often of cranial nerves VI and VII but sometimes including III, IV, IX, and/or X, as well as long tract signs like hemiparesis.

Question 335

Types of ocular allergy

Answer 335

Seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC), and giant papillary conjunctivitis (GPC). VKC and AKC are chronic, bilateral, and severe forms of allergic inflammation affecting the ocular surface. These two relatively uncommon types of allergic eye disease can cause severe damage to the ocular surface, leading to corneal scarring/ulceration and vision loss if not treated properly (this occurs more commonly with AKC than VKC).

Question 336

Vernal keratoconjunctivitis

Answer 336

A type of ocular allergy. Pruritis (all patients) +/- photophobia, thick mucus discharge, pain, blurred vision. Bilateral eye involvement and presence of giant cobblestone-like papillae on the upper tarsal conjunctiva (conjunctiva lining the upper eyelid) are nearly universal findings in patients with VKC. Horner-Trantas dots are another sign. Corneal shield ulcers are a vision-threatening complication of VKC.

Question 337

West syndrome

Answer 337

Infantile spasms Hypsarrhythmia Arrest of psychomotor development Present <12mo, clusters brief contractions (flex/ext) especially on wakening. Poor prognosis Treat with steroids, unless tuberous sclerosis then treat with vigabatrin Broad aetiology - TS, T21, many others

Question 338

Lennox-Gastaut

Answer 338

The eponym "Lennox-Gastaut" syndrome is appropriate for a patient who has slow spike-wave activity in the EEG, exhibits mental retardation, and has intractable seizures of various types. ``` 2-8yo Multiple seizure types Frequent drop attacks Slow spike and wave <2.5Hz on EEG ID ``` Rx: valproate and benzodiazepines

Question 339

Slow spike and wave (<2.5Hz)

Answer 339

Lennox Gastaut

Question 340

Dravet syndrome

Answer 340

AKA severe myoclonic epilepsy of infancy Present 1st year of life with prolonged/complex febrile seizures Initially normal development and EEG, then at 1-4 years developmental arrest and develop other seizure types. ID EEG slows, generalised polyspike Generally drug resistant EEG: slow + generalised polyspike

Question 341

3 Hz and spike-wave

Answer 341

Absence seizures | Provoked by hyperventilation

Question 342

Centro-temporal spikes/ Rolandic spikes

Answer 342

Benign (focal) epilepsy of childhood with centrotemporal spikes (BECTS) AKA benign rolandic epilepsy

Question 343

Juvenile myoclonic epilepsy

Answer 343

Myoclonus, GTC, absence Onset in adolescence Myoclonic seizures on wakening from sleep Treat with valproate (90% respond). Carbamazepine may exacerbate. EEG: 4-6Hz polyspike wave bursts provoked by photic stimulation.

Question 344

Childhood epilepsy with centrotemporal spikes

Answer 344

AKA benign rolandic epilepsy 4-10yo, common (10-15% of epilepsy). Focal sensorimotor seizures from sleep, involve face and tongue, +/- GTC Predominantly nocturnal partial seizures. Normal exam and development, excellent prognosis, remit by mid-teens. Not all are treated (carbamazepine, midazolam). Benign (childhood) epilepsy with centrotemporal spikes (BCECTS or BECTS), also known as rolandic epilepsy, is the most common type of focal epilepsy affecting children; it makes up approximately 10 to 20 percent of all childhood epilepsies.

Question 345

EEG: 4-6Hz polyspike wave bursts provoked by photic stimulation

Answer 345

Juvenile myoclonic epilepsy

Question 346

Landau-Kleffner syndrome

Answer 346

Acquired epileptic aphasia, regression in language 2-8yo Marked behavioural disturbance EEG: continuous status epilepticus of sleep Difficult to treat

Question 347

EEG: continuous status epilepticus of sleep

Answer 347

Landau-Kleffner syndrome

Question 348

AED side effects: visual field constriction

Answer 348

Vigabatrin

Question 349

AED side effects: SJS/TEN

Answer 349

Lamotrigine (1 in 100) -> slow titration CBMZ a/w HLA-B*1502, Chinese, Thai

Question 350

AED side effects: teratogenicity

Answer 350

All (NTD) but especially valproate has highest risk

Question 351

EEG: occipital spike and slow wave

Answer 351

Benign occipital epilepsy

Question 352

Type 1 hypersensitivity

Answer 352

IgE mediated Mast cell degranulation Conditions: asthma, food allergy, hayfever, anaphylaxis

Question 353

Type 2 hypersensitivity

Answer 353

IgG/IgM cytotoxicity (cell surface target/antigen) Altered signalling, complement activation Conditions: haemolysis

Question 354

Type 3 hypersensitivity

Answer 354

Ab-Ag complexes, IgG (soluble antigen) Immune complexes Conditions: serum sickness, dermatitis, erythema nodosum

Question 355

Type 4 hypersensitivity

Answer 355

T cell mediated, delayed Mechanism: Th1, Th2, cytotoxic T cells Conditions: contact conditions, tuberculin, chronic asthma

Question 356

Mnemonic for types of hypersensitivity

Answer 356

ACID Anaphylaxis Cytotoxic Immune complex Delayed

Question 357

Adjustment disorder

Answer 357

A. The development of emotional or behavioral symptoms in response to an identifiable stressor(s) occurring within 3 months of the onset of the stressor(s). B. These symptoms or behaviors are clinically significant, as evidenced by one or both of the following: 1. Marked distress that is out of proportion to the severity or intensity of the stressor 2. Significant impairment in social, occupational, or other important areas of functioning. C. The stress-related disturbance does not meet the criteria for another mental disorder and is not merely an exacerbation of a preexisting mental disorder. D. The symptoms do not represent normal bereavement. E. Once the stressor or its consequences have terminated, the symptoms do not persist for more than an additional 6 months. Specifiers: with depressed mood, with anxiety, with disturbance of conduct, mixed, unspecified

Question 358

Differentiate HLHS from critical AS

Answer 358

HLHS has no murmur Both present with circulatory collapse with ductal closure (hours-days). AS: ejection click, harsh murmur, reduced peripheral perfusion and pulses HLHS: critically ill w/i hours to days, tachypnoea, dyspnoea, crackles, weak pulses, single S2, no murmur

Question 359

Truncus arteriosus

Answer 359

Think of 22q11 Hx: - cyanosis may be seen immediately - CHF develops days-weeks - dyspnoea, FTT, resp infections Ex: - varying degrees of cyanosis and CHF with tachypnoea and dyspnoea - bounding pulses - systolic click - systolic and diastolic murmur Ix: - ECG = normal QRS, BVH - CXR = cardiomegaly, plethora

Question 360

Catalase positive organisms

Answer 360

Mnemonic: SPACE ``` Staphylococcus Pseudomonas Aspergillus Candida Enterobacter ```

Question 361

AED: Carbamazepine

Answer 361

A first-line choice for focal seizures, focal seizures which become bilateral convulsive seizures, and Childhood epilepsy with Centro temporal spikes. Carbamazepine may worsen seizures in the primary generalised epilepsies such as CAE and JME. Side effects: Incoordination (e.g. gait unsteadiness) or drowsiness can occur when a patient first starts carbamazepine. These are usually transient. Rash: in particular Steven-Johnsons Syndrome (SJS), is the most important adverse effect to watch for (esp HLAB*1502, Han Chinese, Thai).

Question 362

AED: Ethosuximide

Answer 362

There is now class 1 evidence for efficacy in CAE (childhood absence epilepsy) and it is regarded as the drug of choice. The main side effect is GI symptoms (abdominal pain). Others: hiccups, joint pain.

Question 363

AED: Lamotrigine

Answer 363

Lamotrigine is most commonly used in generalised epilepsies. It has also been shown to be efficacious in focal seizure disorders. The PBS indication is for epileptic seizures with the following clinical criteria: The condition must have failed to be controlled satisfactorily by other anti-epileptic drugs; OR Patient must be a woman of childbearing potential. Care must be taken when combined with valproate (see later section). Lamotrigine was found to be less efficacious than sodium valproate and ethosuximide in Childhood Absence Epilepsy. Rash is the most serious side effect to monitor. Steven Johnson Syndrome. Patients often feel better on lamotrigine as it is a mood stabiliser.

Question 364

AEDs: Lamotrigine + Valproate

Answer 364

There is a significant synergistic drug interaction with valproate (valproate is an enzyme inhibitor, lamotrigine clearance is reduced and thus lamotrigine levels are higher). This can increase risk of rash significantly. Lower doses of lamotrigine and slow escalation are required.

Question 365

Myasthenia gravis

Answer 365

Most common disorder of NMJ. D/T antibodies against post synaptic acetylcholine receptors. Onset >1 yo. Adolescent girls most common. Extraocular muscles first -> PTOSIS Fatiguability Rx - Anticholinesterasedrugs, immunosuppressants - Thymectomy - PLEX, IVIG

Question 366

AED: Valproate

Answer 366

A good ‘all rounder’. Often used first line in genetic generalised epilepsies (e.g. CAE, JAE, JME) and can be effective in Childhood Epilepsy with Centro temporal spikes and in refractory epilepsies such as Dravet Syndrome. Avoid use in confirmed (or suspected) mitochondrial disorders. In the very young (<2 years old), consider the risk of hepatotoxicity. The aetiology of the neurological problem is helpful in deciding whether to use or not. There are significant concerns regarding teratogenicity and all women of child bearing age must be alerted to this. Appetite and weight gain (very common and can be intolerable). Hepatotoxicity is idiosyncratic and those at most risk are children under the age of 2, metabolic aetiology, and/or multiple drugs, avoid mitochondrial disorders

Question 367

Gitelman syndrome

Answer 367

Inborn AR defect of distal tubule NaCl cotransporter. Often asymptomatic. Transient episodes of weakness and tetany with abdo pain and vomiting. Hypokalaemic metabolic alkalosis. Raised RAAS. HYPOMAGNESAEMIA. Hypocalciuria.

Question 368

AED side effects: hyponatraemia

Answer 368

Oxcarbazepine Carbamazepine Oxcarbazepine is a structural analog of carbamazepine that follows a different metabolic pathway (different metabolites).

Question 369

Anti-NMDA receptor encephalitis

Answer 369

Antibodies to N-methyl-D-aspartate receptor. Usually preceded by intercurrent illness, sometimes a/w Mycoplasma. Movement disorder (chorea, dystonia) Autonomic instability Neuropsychiatric symptoms Seizures Rx: immunomodulation e.g. steroids, IVIG, PLEX, cyclophosphamide, rituximab.

Question 370

ADEM

Answer 370

Acute disseminated encephalomyelitis (ADEM), also known as postinfectious encephalomyelitis, is a demyelinating disease of the central nervous system that typically presents as a monophasic disorder associated with multifocal neurologic symptoms and encephalopathy. ADEM is an uncommon illness; the estimated annual incidence is 0.2 to 0.5 per 100,000 children. The average age of onset in children is between 3 to 7 years. Classic ADEM: - Preceding febrile illness - Symptom onset 4-13 days afterwards - Fever, headache, vomiting, and meningismus - Encephalopathy (REQUIRED) - Multifocal neuro deficits, progress over 4-7 days When to suspect ADEM — The diagnosis should be suspected in a child who develops multifocal neurologic abnormalities with encephalopathy (eg, confusion, excessive irritability, or altered level of consciousness), particularly if onset occurs within two weeks after a viral infection. The mainstay of treatment for ADEM is high-dose intravenous glucocorticoids. Additional options include intravenous immune globulin and plasma exchange.

Question 371

Myotonic dystrophy

Answer 371

Common. AD. Two types, DM1 and DM2. CTG triplet repeat. - Skeletal muscle weakness and myotonia (abnormally slow or delayed muscle relaxation following normal muscle contraction with a characteristic neurophysiologic signature on electromyographic [EMG] testing) - Cardiac conduction abnormalities - Cataracts

Question 372

ESBL organisms

Answer 372

Mainly Klebsiella and E. coli. Also Proteus, Pseudomonas, Enterobacter, Serratia, Salmonella, Yersinia, Shigella. Inducible enzymes carried on plasmids

Question 373

Polydactylyl

Answer 373

Most common congenital digital anomaly of the hand and foot. May be in isolation - Tends to be autosomal dominant May be syndromic - Tends to be autosomal recessive ``` Ulnar Polydactyly associated with: Meckel Syndrome Ellis-Van-Creveld Syndrome T21 Smith Lemli Optiz ``` Radial Polydactyly associated with: Holt Oram Syndrome Fanconi Anaemia

Question 374

Guillain-Barre syndrome

Answer 374

Acute demyelinating disease of peripheral nerves characterised by progressive weakness. Usually post viral/immunisation. Sudden onset weakness, usually lower limbs. Ascending paralysis. Symmetrical. Pain often a prominent feature. 50% have sensory involvement. Respiratory muscle weakness may occur. Ix: - High CSF protein - Slowed motor neuron conduction velocity - Conduction block Deteriorate 10-20 days then plateau. Recovery. 2-3% mortality. Treatment is symptomatic/supportive. Consider plasma exchange, IVIg.

Question 375

Myasthenia gravis

Answer 375

Most common disorder of NMJ. D/T antibodies against post synaptic acetylcholine receptors. Onset >1 yo. Adolescent girls most common. Extraocular muscles first -> PTOSIS Fatiguability Rx - Anticholinesterasedrugs, immunosuppressants - Thymectomy - PLEX, IVIG

Question 376

Bartter syndrome

Answer 376

Inborn AR defect in Na/K/2Cl cotransporter in thick ascneding loop of Henle -> NaCl and water wasting. Polyuria, polydipsia, dehydration, FTT, constipation. ECF contraction -> increased renin/aldosterone -> Na+H2O resorption and K and H secretion. Normal BP. Hypochloraemic, hypokalaemic, alkalosis. Inappropriately high urinary NaCl levels. Elevated urine Ca. Rx with K supps and prostaglandin inhibitors (NSAIDs).

Question 377

Gitelman syndrome

Answer 377

Inborn AR defect of distal tubule NaCl cotransporter. Often asymptomatic. Transient episodes of weakness and tetany with abdo pain and vomiting. ``` Hypokalaemic metabolic alkalosis. Raised RAAS. HYPOMAGNESAEMIA. Hypocalciuria. High urinary chloride excretion – Fractional excretion of chloride >0.5 percent. ```

Question 378

Ataxia ddx

Answer 378

``` Post viral Occult neuroblastoma Drugs (carbamazepine, phenytoin, benzos, antihistamines) Posterior fossa tumour Migraine Ataxia-telangiectasia Friedreich ataxia ```

Question 379

Costello syndrome

Answer 379

Rasopathy ``` FTT (infancy) Characteristic hands*** - Loose skin - Typical hand/ wrist position - Lots of redundant skin - Deep palmar creases ``` High Risk Solid Malignancy (10-15%)

Question 380

Kartagener syndrome

Answer 380

Situs inversus + chronic sinusitis + bronchiectasis Absent dynein arms

Question 381

Surfactant deficiencies

Answer 381

ABCD mnemonic from lecture: ``` A is for acceptable - rarely seen by resp physicians B is for bad - RDS from birth - Improves with surfactant, but returns when that wears off - Need transplant ABCA is for About B to C for acuteness - wide range of phenotypes C is for can live - chronic interstitial lung disease type pattern - avg onset 2-3mo of life D is for didn't study (i.e. don't know) ``` Proteins B and C relevant for surface tension (hydrophobic lipoproteins) Proteins A and D relate to immune defence and immunomodulation Produced by type 2 alveolar cells

Question 382

ESBL organisms

Answer 382

Mainly Klebsiella and E. coli

Question 383

Polydactylyl

Answer 383

Most common congenital digital anomaly of the hand and foot. May be in isolation - Tends to be autosomal dominant May be syndromic - Tends to be autosomal recessive ``` Ulnar Polydactyly associated with: Meckel Syndrome Ellis-Van-Creveld Syndrome T21 Smith Lemli Optiz ``` Radial Polydactyly associated with: Holt Oram Syndrome Fanconi Anaemia

Question 384

COL5A1 and 5A2

Answer 384

Ehlers Danlos syndrome

Question 385

Ellis-Van-Creveld Syndrome

Answer 385

AKA chondroectodermal dysplasia 6 finger dwarfism Narrow chest Short ribs Postaxial polydactyly with a complete extra metacarpal Ectodermal dysplasia with hypoplastic nails and teeth Structural heart disease: most common = ASD, single atrium

Question 386

Rasopathies

Answer 386

What are the Rasopathies? Mutation in genes encoding proteins involved in the Ras/MAPK signal transduction pathway ``` Which syndromes are Rasopathies? Neurofibromatosis Noonan Syndrome Costello Syndrome Cardiofaciocutaneous Syndrome ``` ``` What features do they have in common? Dysmorphic and coarse features Intellectual disability Short Cardiac defects +/- Cancer predisposition ```

Question 387

PTPN11

Answer 387

Noonan syndrome

Question 388

Noonan syndrome

Answer 388

Rasopathy PTPN11 Key points: Relatively common cause of short stature – can be treated by growth hormone Screen for brain tumours if treating with GH May occur with NF-1 mutations also Common cardiac: pulmonary stenosis, LVH

Question 389

Costello syndrome

Answer 389

``` FTT (infancy) Characteristic hands*** - Loose skin - Typical hand/ wrist position - Lots of redundant skin - Deep palmar creases ``` High Risk Solid Malignancy (10-15%)

Question 390

Kartagener syndrome

Answer 390

Situs inversus + chronic sinusitis + bronchiectasis

Question 391

CATCH22

Answer 391

``` Cardiac abnormalities Abnormal facies Thymic aplasia/abnormality Cleft palate Hypocalcaemia Chromosome 22 ```

Question 392

Hyperkalaemia ECG

Answer 392

The earliest manifestation of hyperkalaemia is an increase in T wave amplitude. Peaked T waves P wave widening/flattening, PR prolongation Bradyarrhythmias: sinus bradycardia, high-grade AV block with slow junctional and ventricular escape rhythms, slow AF Conduction blocks (bundle branch block, fascicular blocks) QRS widening with bizarre QRS morphology

Question 393

Hypokalaemia ECG

Answer 393

The earliest ECG manifestation of hypokalaemia is a decrease in T wave amplitude. Increased P wave amplitude Prolongation of PR interval Widespread ST depression and T wave flattening/inversion Prominent U waves (best seen in the precordial leads V2-V3) Apparent long QT interval due to fusion of T and U waves (= long QU interval)

Question 394

Midaz for status epilepticus

Answer 394

0. 3mg/kg buccal/IN 0. 15mg/kg IM/IV Max 10mg.

Question 395

Desmopressin in vWD/platelet disorders

Answer 395

DDAVP releases endogenous VWF from the endothelium. DDAVP is appropriate for treating minor bleeding or for minor surgical procedures in individuals >2 years of age with VWD (typically mild to moderate type 1 and some type 2) and who have previously demonstrated an adequate response in a DDAVP trial. A response is typically considered to have occurred if there is an increase in VWF activity and factor VIII activity to at least >30 international unit (IU)/dL (ideally >50 IU/dL) that persists for more than four to six hours. DDAVP is not used in the following: ●Children <2 years, due to serious side effects in this age group ●Individuals with type 3 VWD, due to lack of response ●Individuals with lack of response in a DDAVP trial ●Individuals with cardiovascular disease, due to an increased risk of thrombosis Great care should be taken if administering DDAVP to individuals with a seizure disorder due to the potential risk of hyponatremia. Treatment with DDAVP has been reported to be effective in preventing bleeding after dental extraction and minor surgery in patients with milder platelet defects, including storage pool disease.

Question 396

vWF/vWD

Answer 396

Von Willebrand factor (VWF) is a large multimeric glycoprotein that performs two critical functions in primary hemostasis: it acts as a bridging molecule at sites of vascular injury for normal platelet adhesion, and under high shear conditions, it promotes platelet aggregation. VWF has a third function that is important in fibrin formation, acting as a carrier for factor VIII in the circulation that maintains the normal level of factor VIII by decreasing the clearance of factor VIII fivefold. A bleeding disorder called von Willebrand disease (VWD) occurs when VWF is deficient or qualitatively abnormal. Mild to moderate mucocutaneous bleeding is most common in types 1 and 2. Severe bleeding is more common with types 2 and 3.

Question 397

Cohort study

Answer 397

Observational (no intervention). Prospective. Categorise currently healthy individuals according to some feature (alcohol, smoking, diet) and follow the groups forward in time to see whether one is more likely to develop disease.

Question 398

Case-control study

Answer 398

Observation (no intervention). Retrospective. Compared diseased and healthy groups and look back in time to see what they have done differently in the past that may have led to disease.

Question 399

Cross-sectional study

Answer 399

Observational. Present time point. Consider differences between groups at a single point in time currently.

Question 400

Cross over study

Answer 400

Each patient receives treatment AND placebo in a random order (compared with parallel trials). Removes many between-patient confounders. Only suitable for chronic disorders that are not cured but for which treatment gives temporary relief.

Question 401

Intention-to-treat analysis

Answer 401

Basically sticking with the original trial groups regardless of compliance with whichever arm the patient was allocated to. More realistic.

Question 402

Ecological studies

Answer 402

Comparing between different regions/countries.

Question 403

Sampling bias

Answer 403

Some members of the eligible population are more likely to be included in the sample than others.

Question 404

Recall bias

Answer 404

One group is more likely to recall events than the other. Often a problem for case-control studies.

Question 405

Publication bias

Answer 405

Important when considering systematic reviews. | Process whereby some studies are more likely to be published, e.g. the ones demonstrating significant difference.

Question 406

Relative risk

Answer 406

The proportion in one group divided by the proportion in the other group = relative difference/relative risk/risk ratio. A value of 1 indicates no difference.

Question 407

Odds ratio

Answer 407

An approximation to the relative risk for case-control studies.

Question 408

Type 1 error

Answer 408

False positive. | Rejecting the null hypothesis when it is actually true, i.e. interpreting results as significant when they are not.

Question 409

Type 2 error

Answer 409

False negative. Accepting the null hypothesis when it is actually false, i.e. interpreting results as insignificant when they are not. Generally "fix" with power/more numbers.

Question 410

Tests to compare binary outcomes between two groups

Answer 410

Chi-squared | Fisher exact test

Question 411

Tests to compare numeric, normally distributed outcomes

Answer 411

T test | Paired t test if samples are paired/matched

Question 412

Tests to compare numeric, non normally distributed outcomes

Answer 412

Mann-Whitney U-test

Question 413

Test to compare normally distributed numeric outcome between more than two groups

Answer 413

Analysis of variance (ANOVA)

Question 414

Regression analysis

Answer 414

Used if adjustment is to be made for confounders before comparing the main outcome between groups.

Question 415

Correlation coefficient

Answer 415

AKA Pearson coefficient of linear correlation Denoted by r Indicates how closely points lie to a line Values -1 to 1. 0 = less linear. Correlates linear (parametric) relationship

Question 416

Spearman rank correlation

Answer 416

Correlates non-parametric (non-linear) relationship.

Question 417

Sensitivity

Answer 417

Proportion of true positives identified by the test

Question 418

Specificity

Answer 418

Proportion of true negatives identified by test

Question 419

Positive predictive value

Answer 419

Proportion of those who test positive who actually have the disease PPV and NPV depend on prevalence of the disease

Question 420

Negative predictive value

Answer 420

Proportion of those who test negative who do not have the disease PPV and NPV depend on prevalence of the disease

Question 421

Likelihood ratios

Answer 421

Compare the probability of the test result given the individual HAS the disease, to the probability if the DON'T have it. Calculated from sensitivity and specificity. Not dependent on prevalence. LR positive result = sens/(1-spec) LR negative result = (1-sens)/spec

Question 422

Post test odds

Answer 422

= likelihood ratio x pretest odds

Question 423

Anaphylaxis adrenaline dose

Answer 423

10mcg/kg | 0.01mL/kg 1:1000 IM (0.1mL/kg 1:10,000 but not really used IM more IV).

Question 424

HEEADSSS acronym

Answer 424

``` Home Education and employment Eating and exercise Activities Drugs and alcohol Sexuality/gender Self harm, suicide, depression Safety ```

Question 425

Inheritance of complete androgen insensitivity

Answer 425

X-linked recessive

Question 426

Androgen insensitivity

Answer 426

Loss-of-function mutations of the gene that encodes the androgen receptor (AR) result in androgen insensitivity syndrome (AIS) in 46,XY individuals with functional testes and unhindered testosterone formation. AIS encompasses a clinical continuum of decreased to absent androgen effects, varying from a completely female phenotype to a male phenotype with undervirilization or infertility. Complete androgen insensitivity (CAIS): - CAIS often presents in an adolescent or young adult woman seen for primary amenorrhea and found to have little or no axillary and pubic hair. - The clinical presentation may also be at birth or during infancy for inguinal masses (containing testes) or hernias in an otherwise healthy female child. The labia and clitoris are unambiguous, and the vagina is short and blind ending. - Other features include normal-appearing testes, an absent uterus, and a 46,XY karyotype. Partial androgen insensitivity (PAIS) — Less severe defects in androgen action cause a variety of forms of 46,XY disorders (or differences) of sex development (DSD) that vary from women with mild degrees of virilization to fertile but undervirilized men.

Question 427

Aspirin overdose - maximising urinary excretion

Answer 427

Alkalinisation of urine

Question 428

Lissencephaly - timing of abnormality

Answer 428

Neuronal migration

Question 429

Methaemaglobinaemia - enzyme

Answer 429

Cytochrome b5 reductase

Question 430

Congenital toxoplasmosis

Answer 430

Classic triad of congenital toxoplasmosis consists of chorioretinitis, hydrocephalus, and intracranial calcifications (diffuse/nonspecific, cf CMV which is periventricular). Most infants with congenital toxoplasmosis are asymptomatic or without apparent abnormalities at birth.

Question 431

Congenital rubella

Answer 431

Clinical manifestations of CRS include sensorineural deafness, cataracts, cardiac malformations (eg, patent ductus arteriosus, pulmonary artery hypoplasia), and neurologic and endocrinologic sequelae. Neonatal manifestations may include growth retardation, radiolucent bone disease (not pathognomonic of congenital rubella), hepatosplenomegaly, thrombocytopenia, purpuric skin lesions (classically described as "blueberry muffin" lesions that represent extramedullary hematopoiesis), and hyperbilirubinemia.

Question 432

Congenital CMV

Answer 432

Congenital cytomegalovirus (CMV) infection is the leading cause of nonhereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities, including cerebral palsy, intellectual disability, vision impairment, and seizures. At birth, most infants with congenital CMV are asymptomatic, but approximately 10 percent have symptoms. Clinical manifestations include petechiae, jaundice at birth, hepatosplenomegaly, thrombocytopenia, small size for gestational age, microcephaly, intracranial calcifications (PERIVENTRICULAR), sensorineural hearing loss, chorioretinitis, and seizures. Sensorineural hearing loss is the most common sequela of congenital CMV and is detected at birth in approximately one-third of infants with symptomatic disease. Many infants with congenital CMV infection are identified solely on the basis of a failed newborn hearing screen. Delayed-onset hearing loss also occurs, although the risk is lower if antiviral treatment is provided in infancy.

Question 433

Perinatal HSV

Answer 433

Most newborns with perinatally acquired HSV appear normal at birth, although many are born prematurely. HSV infection in newborns usually develops in one of three patterns, which occur with roughly equal frequency: * Localized to the skin, eyes, and mouth * Localized central nervous system (CNS) disease * Disseminated disease involving multiple organs The initial manifestations of CNS disease frequently are nonspecific and include temperature instability, respiratory distress, poor feeding, and lethargy; they may progress quite rapidly to hypotension, jaundice, disseminated intravascular coagulation, apnea, and shock. Vesicular skin lesions may or may not be present and develop late in some patients; the absence of skin lesions complicates recognition of the infection.

Question 434

Congenital varicella syndrome

Answer 434

Most cases of congenital varicella syndrome occur in infants whose mothers were infected between 8 and 20 weeks gestation. Characteristic findings in neonates may include: ●Cutaneous scars, which may be depressed and pigmented in a dermatomal distribution ●Cataracts, chorioretinitis, microphthalmos, nystagmus ●Hypoplastic limbs ●Cortical atrophy and seizures

Question 435

Congenital syphilis

Answer 435

Early congenital syphilis is arbitrarily defined by clinical manifestations with onset before two years of age. Clinical manifestations in untreated infants usually appear by three months of age, most often by five weeks. Approximately 60 to 90 percent of live-born neonates with congenital syphilis are asymptomatic at birth. The presence of signs at birth depends upon the timing of intrauterine infection and treatment. Among symptomatic infants, the most common findings include: ``` ●Hepatomegaly ●Jaundice ●Nasal discharge ("snuffles") ●Rash ●Generalized lymphadenopathy ●Skeletal abnormalities ```

Question 436

FGFR3

Answer 436

Achondroplasia

Question 437

Rhizomelic shortening

Answer 437

Long bone shortening that affects the proximal aspects of the upper and lower extremities

Question 438

Achondroplasia complications

Answer 438

``` Recurrent otitis media Obstructive sleep apnoea Obesity Leg bowing Spinal canal stenosis Cervical medullary compression ```

Question 439

Goldenhar syndrome

Answer 439

AKA ocular-auricular-vertebral syndrome (OAVS) Part of craniofacial microsomia spectrum Defect in 1st and 2nd branchial arch

Question 440

Carpenter syndrome

Answer 440

Craniosynostosis: Coronal and other = CLOVER HEAD Prominent metopic ridge Polydactyly Syndactyly of hands and feet ID Cardiac anomalies common: VSD, PDA, PS, TGA, ASD, TOF

Question 441

Wiskott-Aldrich syndrome

Answer 441

X-linked disorder WASP gene Combined B and T cell defects (and neutrophils) ***Poor antibody responses to CHO antigens Investigations Thrombocytopenia (microthrombocytopenia - small plts) Antibodies – often elevated IgE and low IgM Esosinophilia Absent antibody response to CHO antigen ``` TIME: T – thrombocytopenia (micro!) I – immune deficiency (recurrent sinopulmonary infections) M – malignancy (lymphoma/leukemia) E – eczema ```

Question 442

Smith Lemli Opitz

Answer 442

Defect in cholesterol biosynthetic enzyme (C7-reductase) -> required to convert 7-dehydrocholesterol to cholesterol ``` Clinical features Micrognathia Low set posteriorly rotated ears Syndactyly of the second and third toes Males – ambiguous genitalia or female genitalia Adrenal insufficiency (most) ```

Question 443

Holt Oram

Answer 443

Key points: CARDIAC PROBLEMS SKELETAL PROBLEMS (radio-ray, thumb, radius) NORMAL PLATELETS

Question 444

Prune belly syndrome

Answer 444

Triad: - Abdominal muscle deficiency - Severe urinary tract abnormalities - Bilateral cryptorchidism in males

Question 445

Telomere biology disorders

Answer 445

Dyskeratosis congenita (DC) is an inherited disorder characterized by bone marrow failure (BMF), cancer predisposition, and somatic (nonhematologic) abnormalities. DC and related telomere biology disorders (TBD) are caused by mutations that interfere with normal maintenance of telomeres, the regions at the ends of the chromosomes that protect nucleated cells from the loss or gain of genetic material. The following syndromes are considered to be forms of DC: - Hoyeraal-Hreidarsson syndrome - Revesz syndrome - Coats plus syndrome

Question 446

Atypical SUFE

Answer 446

Additional risk factors include renal failure, history of radiation therapy, endocrine abnormalities (particularly hypothyroidism and growth hormone deficiency), and various genetic disorders (eg, Down and Rubenstein-Taybi syndromes). When SCFE occurs in association with one of these additional risk factors, it is called atypical SCFE. Children presenting with SCFE who are younger than 10 years, older than 16 years, whose weight is <50th percentile for age, or whose height is <10th percentile for age should be considered atypical and are likely to have one of the conditions mentioned above

Question 447

Anderson Tawil syndrome

Answer 447

Hypokalemic periodic paralysis with cardiac arrhythmia, is a rare autosomal dominant disorder characterized by episodes of paralysis, ventricular arrhythmias, and dysmorphic features.

Question 448

Myopathies affecting the extraocular muscles

Answer 448

``` Most generalized myopathies do not affect the extraocular muscles. However, there are some notable exceptions. Chronic progressive external ophthalmoplegia (CPEO) is a nonspecific term that is used to describe a range of myopathies that affect the extraocular muscles. These progressive ophthalmoplegias include: ●Isolated CPEO ●Kearns-Sayre syndrome ●Oculopharyngeal muscular dystrophy ●Myotonic dystrophy ●Myotubular myopathy ``` The extraocular muscles often are involved in the mitochondrial myopathies, such as Kearns-Sayre syndrome [1]. Mitochondrial myopathies also can manifest with facial, bulbar, and limb myopathy; neurologic findings (eg, ataxia, spasticity, peripheral neuropathy, deafness, dementia); other ocular findings (eg, optic atrophy, pigmentary degeneration of retina); cardiac conduction abnormalities; gastrointestinal motility; and endocrine, skin, and skeletal abnormalities. Kearns-Sayre syndrome is a mitochondrial cytopathy that is characterized by CPEO, retinal pigmentary changes, and heart block.

Question 449

Gestational alloimmune liver disease

Answer 449

Gestational alloimmune liver disease (GALD) is caused by transplacental passage of reactive maternal immunoglobulins. It was previously known as neonatal hemochromatosis or neonatal iron storage disease, but those terms are misleading because the disorder is unrelated to hereditary hemochromatosis and iron deposition is a consequence, rather than a cause, of the liver injury. Clinical presentation – GALD is characterized by hepatic failure and hepatic and extrahepatic iron accumulation (hemosiderosis) during the neonatal period. The onset is intrauterine, and newborns present with signs of severe liver failure, including coagulopathy, ascites, and hypoalbuminemia. Hyperbilirubinemia typically is both conjugated and unconjugated, although conjugated bilirubin levels may be only modestly elevated. Hepatic cirrhosis in the neonate is common, underscoring the antenatal timing of the hepatic insult. Characteristic clinical features of GALD include refractory hypoglycemia, severe coagulopathy, hypoalbuminemia, elevated serum ferritin (>1000 ng/mL), and ascites. Strikingly, serum aminotransferase levels are normal or near-normal, which helps to distinguish GALD from other causes of liver failure that present during the neonatal period. Antenatal therapy – For pregnant women with a previous pregnancy that resulted in an infant with GALD, antenatal therapy with high-dose intravenous immunoglobulin (IVIG) dramatically reduces the risk for recurrence of disease and also reduces the risk for fetal loss. Postnatal management – The combination of exchange transfusion and IVIG is the current treatment of choice for neonates with GALD. Liver transplantation remains an option for infants who do not respond to IVIG treatment.

Question 450

HLH

Answer 450

The disorder is most commonly diagnosed in the first five years of life but can present in adolescence or adulthood. It is characterized by fever, hepatosplenomegaly, marked elevation in serum aminotransferase levels, cytopenias, hypertriglyceridemia, hyperferritinemia (serum ferritin concentrations are often over 5000 ng/mL), hypofibrinogenemia, and elevated levels of soluble IL-2 receptor alpha (sCD25).

Question 451

Juvenile polyps

Answer 451

Juvenile polyps are benign hamartomas, which typically occur between the ages of 2 and 10 years, with a peak at three to four years. Patients usually present with painless rectal bleeding, with or without mucus; a few may have lower abdominal pain from traction on the polyp. May have raised calprotectin - can only differentiate from IBD with scope.

Question 452

Electrical alternans

Answer 452

Consecutive, normally-conducted QRS complexes that alternate in height Occurs when the heart swings backwards and forwards within a large fluid-filled pericardium Urgent TTE ?tamponade

Question 453

ECG findings pericardial effusion

Answer 453

Low QRS voltages Tachycardia Electrical alternans

Question 454

SCID phenotypes

Answer 454

All have no T cells (T-) ``` B+ and NK- - AR: JAK3, common gamma chain - X linked B+ NK+ = IL-7alpha def B- NK- = ADA/ADK2 B-NK+ = RAG1/2, Artemis ```

Question 455

Absent nasal bone antenatally

Answer 455

Trisomy 21 Also a/w T18 and T13 but less commonly.

Question 456

Immunodeficiency patterns: Bacteria Sinopulmonary Otitis media

Answer 456

B cells

Question 457

Immunodeficiency patterns: Everything! Candidiasis Any location

Answer 457

T cells

Question 458

Immunodeficiency patterns: Encapsulated bacteria Sinopulmonary

Answer 458

Complement

Question 459

Immunodeficiency patterns: Bacteria, fungi Skin, nodes, deep abscesses

Answer 459

Neutrophils

Question 460

Dravet syndrome - contraindicated AEDs

Answer 460

Sodium channel blocking drugs such as carbamazepine and its analogs (oxcarbazepine and eslicarbazepine), lamotrigine, and phenytoin may aggravate seizures in patients with DS and should generally be avoided.

Question 461

Developmental coordination disorder

Answer 461

Developmental coordination disorder (DCD) is characterized by problems with motor coordination that interfere with academic performance and social integration in otherwise healthy children. It typically presents in the early school years and persists into adolescence or adulthood. The diagnosis of DCD is typically made in children between 6 and 12 years of age. Most children with DCD have lifelong delays in achieving motor skills. The DSM-5 criteria for DCD include: ●The achievement and performance of coordinated motor skills is substantially below that expected given the child's chronologic age and opportunity for skill learning and use. ●The poor performance significantly and persistently interferes with activities of daily living appropriate to chronologic age and impacts academic/school productivity, prevocational and vocational activities, leisure, and play. ●The symptoms began in the early developmental period. ●The impairments in motor skills deficits are not better explained by intellectual disability or visual impairment and cannot be attributed to another neurologic or neuromuscular condition affecting movement (eg, cerebral palsy, muscular dystrophy, degenerative disorder). Although age ≥5 years is not a diagnostic criterion, the diagnosis of DCD is rarely made in children <5 years of age.

Question 462

X-linked hypophosphataemic rickets

Answer 462

AKA vitamin D resistant rickets Mutation in PEX gene, X linked Defective phosphate reabsorption Earliest sign -> increased ALP. Plasma phosphate may be normal until 6-9 months. By 12 months, have delayed growth, hypophosphataemia, increased ALP, radiological rickets. Rx: calcitriol and phosphate supplements Cx: hypercalcaemia, nephrocalcinosis

Question 463

Cardiac complication Rett syndrome

Answer 463

Prolonged QTc

Question 464

Which childhood leukaemia is associated with the highest risk of disseminated intravascular coagulation (DIC) at presentation?

Answer 464

Acute promyelocytic leukaemia Acute promyelocytic leukemia (APL) is a rare subtype of AML that is characterized by maturation arrest at the promyelocyte stage and the classic chromosomal translocation t(15;17)(q22;q21). Many patients with APL present with DIC that requires urgent and aggressive management.

Question 465

What is the first-line treatment for paediatric Grave’s disease

Answer 465

Carbimazole

Question 466

What is the mechanism of action of N-acetylcysteine?

Answer 466

It is thought to provide cysteine for glutathione synthesis.

Question 467

ITP indications for BMA

Answer 467

UTD: Important indications for bone marrow aspiration and biopsy include the following: ●Atypical clinical or laboratory features at presentation that suggest malignancy or bone marrow failure as discussed above (eg, especially lymph node enlargement, splenomegaly, bone or joint pain, fevers, weight loss, neutropenia, leukocytosis, atypical lymphocytes, or marked anemia). ●Insufficient or no response to treatment with glucocorticoids, intravenous immune globulin (IVIG), and/or anti-D immune globulin given at appropriate doses. Our practice differs from the 2011 guidelines from the American Society of Hematology (ASH), which state that bone marrow examination is not necessary in children who fail IVIG. ●New findings that emerge during follow-up that are not consistent with ITP (eg, subsequent clinical findings of lymph node enlargement, organomegaly, bone or joint pain, fevers, or new laboratory findings of neutropenia, leukocytosis, or anemia without bleeding) or loss of response to ITP therapies that had previously been effective.

Question 468

X-linked ALD MRI changes

Answer 468

White matter changes with anterior sparing

Question 469

Anaesthesia and myopathies

Answer 469

Central core - malignant hyperthermia Dystrophinopathies - rhabdomyolysis Certain myopathies present life-threatening risks that are specific to anesthesia. These are malignant hyperthermia (MH), anesthesia-induced rhabdomyolysis (AIR), and propofol toxicity. Malignant hyperthermia (MH) is a complex genetic disorder of skeletal muscle typically manifesting clinically as a hypermetabolic crisis when a susceptible individual receives a halogenated inhalational anesthetic agent or succinylcholine. Patients with myopathies caused by RYR1 mutations, notably central core myopathy, are assumed to be MHS. Anesthesia-induced rhabdomyolysis (AIR) is a syndrome that involves skeletal muscle breakdown, resulting in release of myoglobin, elevated serum creatine kinase (CK), and potentially life-threatening hyperkalemia after exposure to succinylcholine or volatile anesthetic agents, primarily in patients with muscular dystrophy (MD).

Question 470

A comparison of parasomnias that occur on arousal from NREM sleep

Answer 470

UTD Table All occur first third of sleep, as non REM sleep. Same frequency, 3-4/week to 1-2/month. EEG: Slow-wave sleep, with rhythmic theta or delta activity. Duration 10-30 minutes. Confusional arousal - 2-10yo - Whimpering, some articulation, sitting up in bed, inconsolable Sleep terrors - 2-10yo - Screaming, agitation, flushed face, sweating, inconsolable Sleep walking - 5-10yo - Walking around the room or house, may be quiet or agitated, unresponsive to verbal commands

Question 471

Catecholaminergic polymorphic VT

Answer 471

Inherited channelopathy, arrhythmogenic disease - RyR2 receptor, AD mutation As common as long QT! Episodic palpitations/syncope/arrest, precipitated by exercise/emotion. Arrhythmia reproducible with exercise stress testing. Worsened by adrenaline. Bidirectional VT = pathognomonic (also seen in dig toxicity).

Question 472

Parotitis

Answer 472

With the exception of mumps, diseases of the salivary glands are rare in children. Bilateral enlargement of the submaxillary glands can occur in HIV/AIDS, cystic fibrosis, Epstein-Barr virus infection, malnutrition, and transiently during acute asthmatic attacks. Chronic vomiting can be accompanied by enlargement of the parotid glands. Benign salivary gland hypertrophy has been associated with endocrinopathies: thyroid disease, diabetes, and Cushing syndrome. Infiltrative disease or tumors are uncommon; red flags include facial nerve palsy, rapid growth, fixed skin, paresthesias, ulceration, or a history of radiation to the head or neck region. Parotitis: Acute parotitis is often caused by blockage, with further inflammation due to bacterial infection. The blockage may be due to a salivary stone or mucous plug. Stones can be removed by physical manipulation, surgery, or lithotripsy. Recurrent parotitis is an idiopathic swelling of the parotid gland that can occur in otherwise healthy children. The swelling is usually unilateral, but both glands can be involved simultaneously or alternately. There is little pain; the swelling is limited to the gland and usually lasts 2-3 wk. Treatment may include local heat, massaging the gland, and antibiotics. Suppurative parotitis is usually caused by Staphylococcus aureus . It is usually unilateral and may be accompanied by fever. The gland becomes swollen, tender, and painful. Suppurative parotitis responds to antibacterial therapy based on culture obtained from the Stensen duct or by surgical drainage. Viral causes of parotitis include mumps (often in epidemics), Epstein-Barr virus, human herpesvirus 6, enteroviruses, and HIV. Sarcoidosis: Symmetric parotid swelling; Heerfordt syndrome when associated with uveitis, fever, and facial palsy. Sjogrens: Recurrent parotid gland enlargement and parotitis are the most common manifestations in children (>70%). Clinical presentation of recurrent parotitis and or recurrent parotid gland swelling in a child or adolescent is characteristic and should raise the suspicion for Sjogren syndrome.

Question 473

Sarcoidosis - lab findings

Answer 473

There is no single standard laboratory test diagnostic of sarcoidosis. Anemia, leukopenia, and eosinophilia may be seen. Other nonspecific findings include hypergammaglobulinemia and elevations in acute-phase reactants, including erythrocyte sedimentation rate and C-reactive protein value. Hypercalcemia and/or hypercalciuria occur in only a small proportion of children with sarcoidosis. Angiotensin-converting enzyme (ACE) is produced by the epithelioid cells of the granuloma, and its serum value may be elevated, but this finding lacks diagnostic sensitivity and specificity. ACE levels are estimated to be elevated in >50% of children with sarcoidosis. In addition, ACE values may be difficult to interpret because reference values for serum ACE are age dependent. Fluorodeoxyglucose F 18 positron emission tomography can help identify nonpulmonary sites for a diagnostic biopsy.

Question 474

Sjogren syndrome

Answer 474

Sjogren syndrome is a chronic, inflammatory, autoimmune disease characterized by progressive lymphocytic and plasma cell infiltration of the exocrine glands, especially salivary and lacrimal, with potential for systemic manifestations. It is rare in children and predominantly affects middle-age women with classic symptoms of dry eyes (keratoconjunctivitis sicca ) and dry mouth (xerostomia). Recurrent parotid gland enlargement and parotitis are the most common manifestations in children (>70%). Clinical presentation of recurrent parotitis and or recurrent parotid gland swelling in a child or adolescent is characteristic and should raise the suspicion for Sjogren syndrome. IMMUNOLOGIC ABNORMALITIES Presence of at least 1 of the following antibodies: anti-SSA, anti-SSB, high-titer antinuclear antibody, rheumatoid factor.

Question 475

DDX Sjogrens syndrone / parotitis

Answer 475

The differential diagnosis of Sjogren syndrome in children includes juvenile recurrent parotitis , characterized by intermittent unilateral parotid swelling typically lasting only a few days. It is frequently associated with fever and may undergo remission with puberty. Unlike in Sjogren syndrome, there is a male predominance, juvenile recurrent parotitis is seen in the younger children (3-6 yr), and there is a lack of focal lymphocytic infiltrates on biopsy. Other conditions in the differential diagnosis include eating disorders, infectious parotitis (mumps, streptococcal and staphylococcal infections, Epstein-Barr virus, cytomegalovirus, HIV, parainfluenza, influenza enterovirus), and local trauma to the buccal mucosa.

Question 476

Omenn syndrome

Answer 476

Mutation in RAG 1/2 - enzyme responsible for VDJ recombination and generation of TCR -> Partial protein expression and limited production of T and B cells Outcome: Activated T cells with a limited repertoire and dysregulated B cells SCID phenotype but without lymphopenia ``` Key Features Exfoliative erythroderma +/- Staph infection Loss of hair, eyebrows and alopecia Lymphadenopathy Hepatosplenomegaly Chronic diarrhoea, FTT Lymphocytosis, eosinophilia Elevated IgE ```

Question 477

SCID phenotype but without lymphopenia

Answer 477

Omenn syndrome

Question 478

Fragile X triplet repeat

Answer 478

CGG repeats on FMR1 at Xq27.3 – ‘Congenital Giant Gonads’

Question 479

Benign focal epilepsies of childhood

Answer 479

Benign (self-limited) focal epilepsies of childhood are electroclinical syndromes of unknown or genetic cause that occur in developmentally and neurologically normal children and have a benign course, remitting prior to adulthood. The best-described syndromes are: ●Benign epilepsy with centrotemporal spikes (BECTS), also referred to as rolandic epilepsy ●Early-onset childhood occipital epilepsy (Panayiotopoulos type), often referred to as Panayiotopoulos syndrome ●Late-onset childhood occipital epilepsy (Gastaut type), also referred to as benign occipital epilepsy of childhood or Gastaut syndrome These epilepsy syndromes are distinguished from symptomatic focal epilepsy, which refers to epilepsy that results from brain injury or other structural brain disease. Thus, the benign focal epilepsies of childhood can be viewed as a spectrum of conditions with "functional" or "nonlesional" focal epileptogenicity, each characterized by location, seizure type(s), and electroencephalogram findings

Question 480

Panayiotopoulos syndrome

Answer 480

Early-onset benign childhood occipital epilepsy, often referred to as Panayiotopoulos syndrome, is characterized by a unique seizure type that has prominent autonomic features. Occurring in early childhood, Panayiotopoulos syndrome presents at a mean age of younger than 5 years (range 1 to 14 years). The seizures in this syndrome have a distinctive yet variable phenomenology compared with other focal epilepsy syndromes. Vomiting is the most characteristic and frequent ictal sign, occurring in 70 to 85 percent of patients. Vomiting. Syncope. Visual changes. The seizures are usually nocturnal and last more than five minutes. nterictal electroencephalography (EEG) in Panayiotopoulos syndrome shows occipital spikes in approximately 75 percent of cases. The clinical course of Panayiotopoulos syndrome is usually benign. Seizures are infrequent, and almost half of patients have just a single seizure. Spontaneous remission usually occurs within two to three years from onset.

Question 481

LATE-ONSET CHILDHOOD OCCIPITAL EPILEPSY (GASTAUT TYPE)

Answer 481

Late-onset childhood occipital epilepsy is also referred to as benign occipital epilepsy of childhood or Gastaut syndrome. Late-onset childhood occipital epilepsy has a mean age of presentation of 8 to 9 years (range 3 to 16 years), which is somewhat later than in Panayiotopoulos syndrome. Seizures often include visual symptoms, either blindness or elementary visual hallucinations. Compared with Panayiotopoulos syndrome, seizures are more frequent and of shorter duration, usually less than five minutes. Most seizures occur in the daytime. Less benign than Panayiotopoulos syndrome.

Question 482

Post infectious neutropenia

Answer 482

Infectious neutropenias may represent the most common cause of acquired isolated neutropenia. A number of bacterial, viral, parasitic and rickettsial infections are responsible. In most instances, particularly with viral infections, the neutropenia is short-lived and rarely results in bacterial superinfection. Mechanisms include redistribution, sequestration and aggregation, and destruction by circulating antibodies. Hepatitis B virus, Epstein-Barr virus and human immunodeficiency virus can be associated with more severe and protracted neutropenia.

Question 483

DDX neutropenia

Answer 483

Post infectious (most common) Drug induced (2nd) Nutritional (B12, folate, copper) Immune neutropenia Pure white cell aplasia (a/w thymoma) Hypersplenism (splenomegaly from any aetiology) Marrow disorders (aplastic anaemia, leukaemia, chemotherapy) Congenital (These syndromes include severe infantile agranulocytosis, myelokathexis, Shwachman-Diamond-Oski syndrome, Chediak-Higashi syndrome, and reticular dysgenesis) Cyclic neutropenia is characterized by recurrent mouth infections and regular oscillations in the numbers of blood neutrophils, monocytes, eosinophils, lymphocytes and reticulocytes at approximately 21-day intervals. Myeloperoxidase deficiency — In many clinical laboratories, neutrophils are identified on the white blood cell differential by virtue of their positivity for myeloperoxidase. Patients with myeloperoxidase deficiency may then be erroneously considered as having severe neutropenia.

Question 484

Kostman syndrome

Answer 484

Severe congenital neutropenia The term "congenital neutropenia" primarily refers to severe congenital neutropenia (SCN), with the Kostmann Syndrome (HAX1 mutation) as one subtype. Genetics and pathogenesis — SCN is a genetically transmitted disorder with recessive, dominant, or X-linked inheritance depending on which mutation is responsible: ●SCN due to mutations in the gene for neutrophil elastase (ELANE, previously called ELA2) is an autosomal dominant condition and occurs in 50 to 60 percent of patients ●The initial family described by Kostmann, as well as other more recently described kindreds, have mutations in HAX1 with autosomal recessive inheritance ●X-linked inheritance is seen in SCN due to mutations in the Wiskott-Aldrich syndrome (WAS) gene, also called WASP

Question 485

ELANE

Answer 485

Gene for neutrophil elastase | Severe congenital neutropenia (50-60%)

Question 486

Most common suppurative complication of acute otitis media (AOM)

Answer 486

Mastoiditis

Question 487

Dacrocystitis (and dacroadenitis)

Answer 487

Infantile dacryocystitis is a painful, tender swelling of the inferior medial canthal area, with surrounding cellulitis. Dacryoadenitis is inflammation of the lacrimal glands (superolateral), whereas dacryocystitis is inflammation of the lacrimal sac (inferomedial) in the inferior lid.

Question 488

"Most significant differential power" for RA vs LA isomerism (as per Parks)

Answer 488

IVC - Asplenia (RA isomerism): almost always normal - Polysplenia (LA): interrupted with azygous continuation Cardiovascular malformations generally more severe in asplenia. TAPVR more common asplenia. Common/single AV valve more common asplenia, plus ASD (primum>secundum) TGA more common asplenia. >95% first year mortality in asplenia (fulminating sepsis is one cause).

Question 489

Netherton syndrome

Answer 489

Trichorrhexis invaginata of hair is also known as "bamboo hair" and is pathognomonic of Netherton syndrome. Netherton syndrome is a severe disorder of cornification caused by (SPINK5) mutations. Menkes disease is also known as ‘kinky hair disease’ but is not associated with eczema, recurrent infections or raised IgE. Children present with seizures and development delay due to genetic disorder leading to severe copper deficiency (Menkes). Netherton syndrome is a rare autosomal recessive disorder of cornification caused by mutations in the serine protease inhibitor of Kazal type 5 gene (SPINK5), which encodes a serine protease inhibitor expressed in epithelial and mucosal surfaces. NS is clinically characterized by the classic triad of congenital ichthyosiform erythroderma, a specific hair shaft abnormality termed trichorrhexis invaginata ("bamboo hair"), and an atopic diathesis. NS is one of the most severe disorders of cornification. Infants typically present at birth with a generalized scaling erythroderma and have a high risk of life-threatening complications, such as hypernatremic dehydration, failure to thrive, and sepsis. In older children, a wide range of allergic manifestations may occur, including severe atopic dermatitis, asthma, hay fever, and markedly elevated serum levels of immunoglobulin E.

Question 490

Ichthyosis

Answer 490

Ichthyosis is a condition that causes widespread and persistent thick, dry, "fish-scale" skin. The skin of a person with ichthyosis is rough, dry and scaly and needs to be regularly moisturised.

Question 491

Congenital disorders of glycosylation

Answer 491

Congenital disorders of glycosylation (CDGs) are a group of over 100 monogenic human diseases with defects in the synthesis of oligosaccharides. Oligosaccharides, or glycans, are multisugar structures attached to proteins or lipids. Most proteins have glycans attached to them - carbohydrate moieties of glycoproteins. N-Glycans and O-glycans (depending on attachment site). 2 most common are: - CDG 1a (phosphomannomutase deficiency) - CDG 1b (phosphomannoseisomerase deficiency) Most AR. Multiorgan disorders affecting particularly the brain (except CDG 1b which is mainly hepatogastrointestinal). CDG1a dysmorphology - inverted nipples, fat pads - muscular hypotonia - faltering growth - cerebellar hypoplasia Dx: - transferrin isoelectric focusing screens but does not detect all - enzymology on white cells or fibroblasts Rx: - CDG1b: mannose supplementation - others are symptomatic/supportive

Question 492

Macrocephaly ddx

Answer 492

HC>97th centile Increased brain parenchyma (familial, NF, TS, achondroplasia, fragile X, leukodystrophy, lysosomal, organic acid). Increased CSF (hydrocephalus, benign enlargement subarachnoid space). Increased blood (IVH, subdural, epidural, AVM). Increased bone (rare - marrow expansion d/t thalassaemia, skeletal dysplasia). Increased ICP (idiopathic, infection, blood, CSF). Mass.

Question 493

Erythema multiforme

Answer 493

``` Acute immune mediate self limiting symmetrical fixed rash with characteristic target lesions. May involve mucosa. 90% d/t infection - HSV most common. Other causes: - Mycoplasma, EBV, Chlamudia - drugs: sulphonamides, penicillin - CTD: SLE, polyarteritis nodosa - malignancy ```

Question 494

Microcephaly ddx

Answer 494

HC>2SD below mean (<3rd centile). Isolated. Syndromic: Williams, Angelman, Rett, Bloom, Cri du chat, Cornelia de Lange, T21/18/13. Neuroanatomic: NTD, holoprosencephaly, lissencephaly, polymicrogyria. Metabolic: maternal DM/PKU, PKU, methylmalonic aciduria. Environmental: TORCH, meningitis, antenatal drugs, perinatal insult, anoxia/ischaemia.

Question 495

Metabolics: sweet odour

Answer 495

Maple syrup urine disease Especially nappy Block in degradation leucine, isoleucine, valine (BCAAs). Encephalopathy. Seizures.

Question 496

Non-ketotic hyperglycinaemia

Answer 496

Defective glycine cleavage - glycine is a neurotransmitter. Early onset seizure disorder. Increased fetal movements (in utero seizures). Hiccups, hypotoonia. Progressive apnoeas, encephalopathy. Seizures. Developmental delay/psychomotor retardation. Dx: - elevated glycine urine or plasma - increased CSF:plasma glycine ratio - enzymology Rx: - sodium benzoate - dextromethorphan Poor prognosis.

Question 497

``` Along with ectopia lentis, which of the following is a common eye sign seen in Marfan’s syndrome? Cataract Coloboma Glaucoma Myopia ```

Answer 497

Myopia. Ectopia lentis occurs in 50 to 80 percent with MFS. Ectopia lentis is the only cardinal ocular criterion for MFS. The finding of myopia >3 diopters contributes one point to the systemic score.

Question 498

Gender dysphoria or incongruence

Answer 498

Distress or discomfort that may occur if gender identity and birth-designated sex are not congruent.

Question 499

Calculate post test probability

Answer 499

Need pretest probability and likelihood ratios. Pretest ODDS = pretest prob / (1-pre test prob) Post test ODDS = pretest odds x likelihood ratio Post test probability = posttest odds / (1+posttest odds)

Question 500

Anti NMDA receptor encephalitis

Answer 500

Anti-NMDA receptor encephalitis is associated with a predictable set of symptoms that combine to make up a characteristic syndrome. Clinical features — Many patients present with prodromal headache, fever, or a viral-like process, followed in a few days by a multistage progression of symptoms that include: ●Prominent psychiatric manifestations (anxiety, agitation, bizarre behavior, hallucinations, delusions, disorganized thinking, psychosis). ●Sleep disorders, including sleep reduction at disease onset and hypersomnia during recovery. ●Memory deficits. ●Seizures. ●Decreased level of consciousness, stupor with catatonic features. ●Frequent dyskinesias: orofacial, choreoathetoid movements, dystonia, rigidity, opisthotonic postures. ●Autonomic instability: hyperthermia, fluctuations of blood pressure, tachycardia, bradycardia, cardiac pauses, and sometimes hypoventilation requiring mechanical ventilation. ●Language dysfunction: diminished language output, mutism, echolalia. Children as young as eight months have been reported with this syndrome. The diagnosis of anti-NMDA receptor encephalitis is confirmed by the detection of IgG antibodies to the GluN1 (also known as NR1) subunit of the NMDA receptor in CSF (serum is less reliable). The detection of an ovarian teratoma is age dependent; approximately 50 percent of female patients older than 18 years have uni- or bilateral ovarian teratomas, while less than 9 percent of girls younger than 14 years have a teratoma. Treatment consists of immunosuppression and tumor resection when indicated.

Question 501

Medium-chain acyl-CoA dehydrogenase deficiency

Answer 501

Fat oxidation disorder - commonly present with hepatic, cardiac, or muscle symptoms. Most common fat oxidation disorder - 1 in 10k, same as PKU. Mortality rate 25% on first presentation. Hypoketotic hypoglycaemia. Encephalopathy. Hepatomegaly and deranged LFTs. Mean age 15mo, most commonly precipitated by diarrhoea. Commonly G985 mutation. Rx - avoid fasting

Question 502

Long chain defects

Answer 502

Fat oxidation disorder - commonly p/w hepatic, cardiac, muscle symptoms. More severe than medium chain disorders. Hypoketotic hypoglycaemia. Myopathy. Hypertrophic cardiomyopathy. Pigmentary retinopathy, peripheral neuropathy. May have maternal hepatic symptoms in pregnancy (HELLP, AFLP).

Question 503

Refsum disease

Answer 503

Refsum disease is another treatable progressive ataxia. It should be suspected when a patient with autosomal recessive ataxia presents with the additional triad of ichthyosis, retinitis pigmentosa, and neuropathy. Patients with classic Refsum disease are unable to degrade phytanic acid due to deficient activity of phytanoyl-CoA hydroxylase (PhyH) caused by mutations in the PHYH gene. Strict reduction in dietary phytanic acid intake may be associated with a significant improvement in both the peripheral neuropathy and ataxia.

Question 504

Gaucher disease

Answer 504

Glucocerebrosidase deficiency -> accumulation of cerebroside in visceral organs +/- brain. 3 types. - type 1 most common, non neuropathic, splenomegaly>hepatomegaly, anaemia, bleeding tendancy, bone pain/deformities/osteopenia, abdo pain from splenic infarcts - type 2: acute neuropathic, severe CNS involvement and rapidly progressive, HSM, squint/gaze palsy - type 3: subacute neuropathic, squint/gaze palsy, splenomegaly>hepatomegaly, slow neuro deterioration Dx: - elevated ACE, elevated acid phosphatase - BMA: Gaucher cells = crumpled tissue-paper cytoplasm - white cell enzymology Rx: - enzyme replacement therapy effective in type 1 and 3 - splenectomy - no effective treatment type 2

Question 505

Mucopolysacharidoses

Answer 505

Impaired glycosaminoglycan metabolism in lysosomes. Generally normal at birth and present with DD in first year. Types: Hurler, Hunter (XL), Sanfillipo, Morquio, Maroteaux-Lamy, Sly

Question 506

Hurler syndrome

Answer 506

Mucopolysacharidosis - abnormal glycosaminoglycan metabolism. Hurler is the classic MPS with storage affecting body and CNS. Enzyme deficiency: alpha iduronidase. Features - coarse facies, macroglossia, hirsutism, corneal clouding - airway/ENT problems, secretory otitis media - dysostosis multiplex - cardiomyopathy, valve disease - HSM - hernias - stiff joints - DD and retardation Dx: - urine for glycosasminoglycans (screen) - white cell enzymology Rx: - BMA - ERT (limited BBB penetration)

Question 507

Palpable S2

Answer 507

A palpable S2 in the second left intercostal space correlates with pulmonary hypertension. Causes pulmonary HTN (Parks): - increased PBF d/t large LTR shunts - alveolar hypoxia - increased pulmonary venous pressures - primary pulmonary vascular disease - other lung disease

Question 508

CALM descriptors

Answer 508

The irregular borders of the café-au-lait spots in McCune-Albright syndrome are often compared to a map of the coast of Maine. By contrast, café-au-lait spots in other disorders have smooth borders, which are compared to the coast of California.

Question 509

GBS infection neonate/infant

Answer 509

Group B streptococcal (GBS) infection in neonates and young infants is classified by age at onset. ●Early-onset GBS – Early-onset GBS generally presents at or within 24 hours of birth but can occur through day 6 after birth. ●Late-onset GBS – Late-onset GBS usually occurs at four to five weeks of age (range 7 to 89 days). Early-onset disease — Early-onset GBS infection most commonly manifests as generalized sepsis, pneumonia, or meningitis. In >90 percent of cases, clinical signs are apparent in the first 24 hours after birth. Late-onset disease — Late-onset GBS disease most often presents as bacteremia without a focus; however, meningitis and other focal infections can occur.

Question 510

Suprasternal thrill

Answer 510

Aortic stenosis

Question 511

Mid-systolic click

Answer 511

Mitral valve prolapse

Question 512

Complications of vascular ring surgery

Answer 512

Parks: In infants who have had surgery for severe symptoms, airway obstruction may persist for months-1 year. Noisy respiration is caused by pre-existing tracheomalacia. This is more likely in double aortic arch, vascular sling, or right aortic arch with left ligamentum arteriosum.

Question 513

Flexible vs rigid bronchoscopy

Answer 513

Rigid bronchoscopy is a procedure in which a large straight metal tube with a beveled distal end is inserted into the trachea through the mouth. Instruments including a telescope with a light source (with or without video monitoring), forceps, suction catheters, and even flexible bronchoscopes can be placed through the beveled tube. Patients can also be simultaneously ventilated through the rigid system. It requires general anesthesia and is typically used for tumor debulking, airway dilation, foreign body removal, placement or removal of airway stents, or to control massive hemoptysis. Flexible bronchoscopy is more common, and allows deeper exploration of the airways -> better for diagnostics, can also do some procedures. Prev exam Q: rigid bronch for inhaled foreign body.

Question 514

Poor effort spirometry

Answer 514

?suggested by low PEF (peak expiratory flow). The falsely reduced FEV1 and FEV1 /FVC ratio may be misinterpreted as indicating an “obstructive impairment.” However, the shape of the flow-volume curve and the reduced PEF indicate that the low values are caused by poor effort.

Question 515

DRESS

Answer 515

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug-induced hypersensitivity syndrome (DIHS) is a severe idiosyncratic reaction characterized by fever (38 to 40°C), malaise, lymphadenopathy, and skin eruption. Additional systemic symptoms may be related to visceral involvement (eg, liver, kidney, lung). In most patients, the reaction begins two to six weeks after the initiation of the offending medication. The aromatic antiepileptic agents (carbamazepine, phenytoin, lamotrigine, oxcarbazepine, and phenobarbital), allopurinol, and antibacterial sulfonamides are the most frequent causes of this disorder

Question 516

SJS/TEN

Answer 516

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis. Mucous membranes are affected in over 90 percent of patients, usually at two or more distinct sites (ocular, oral, and genital). According to a widely accepted classification, SJS and TEN are considered a disease continuum and are distinguished chiefly by severity, based upon the percentage of body surface affected by blisters and erosions: ●SJS is the less severe condition, in which skin detachment is <10 percent of the body surface. ●TEN involves detachment of >30 percent of the body surface area (BSA). ●SJS/TEN overlap describes patients with skin detachment of 10 to 30 percent of BSA. The risk of SJS/TEN seems to be limited to the first eight weeks of treatment. In children, the medications most often associated with SJS/TEN are sulfonamide antimicrobials, phenobarbital, carbamazepine, and lamotrigine. Infections, including Mycoplasma pneumoniae infection, are the next most common trigger of SJS/TEN, particularly in children. Prodrome — Fever, often exceeding 39°C (102.2°F), and influenza-like symptoms precede by one to three days the development of mucocutaneous lesions. Cutaneous lesions — The skin lesions typically begin with ill-defined, coalescing, erythematous macules with purpuric centers, although many cases of SJS/TEN may present with diffuse erythema. The skin is often tender to the touch, and skin pain can be prominent and out of proportion to the cutaneous findings. As the disease progresses, vesicles and bullae form, and within days the skin begins to slough. Other — Pharyngeal mucosa is affected in nearly all patients; tracheal, bronchial, and esophageal membranes are less frequently involved. Intestinal involvement is rare.

Question 517

Serum sickness/like reaction

Answer 517

The cardinal features of serum sickness are rash, fever, and polyarthralgias or polyarthritis, which begin one to two weeks after the first exposure to the responsible agent and resolve within a few weeks of discontinuation. Although patients may appear very ill and uncomfortable during the acute febrile stage, the disease is self-limited, and prognosis is excellent once the responsible drug is stopped. Serum sickness — The most common signs and symptoms of serum sickness are dermatitis (rash), fever, malaise, and polyarthralgias or polyarthritis.

Question 518

Neonatal hyperinsulinism from maternal GDM

Answer 518

Resolved w/i 2-4 days. Increased glucose utilization primarily results from hyperinsulinism. Excess insulin also suppresses hepatic glucose production. The infant of a diabetic mother is the most common neonatal clinical situation in which hyperinsulinism causes hyperinsulinemic hypoglycemia. In this setting, it is postulated that intermittent maternal hyperglycemia causes fetal hyperglycemia, which leads to hypertrophied and hyperfunctioning beta cells resulting in fetal and neonatal hyperinsulinemia. After termination of the maternal glucose supply at delivery, hypoglycemia from persistent hyperinsulinism in the newborn usually is transient and typically resolves two to four days after birth.

Question 519

X-linked hypophosphataemia

Answer 519

The term vitamin D-resistant rickets (VDRR) originally was used to describe a syndrome of hypophosphatemia and rickets (and/or osteomalacia) that resembled vitamin D deficiency but did not respond to vitamin D replacement or pharmacologic doses of vitamin D. Most of these cases were caused by renal phosphate wasting. X-linked hypophosphatemia is a dominant disorder, and the most common hereditary hypophosphataemia. Skeletal abnormalities, including rickets, osteomalacia, and growth failure, are the major clinical findings in children with XLH. However, it is only at the time of weightbearing that leg deformities (eg, bowing) and progressive departure from normal growth rate become sufficiently striking to attract medical attention. Most children have radiographic evidence of rickets, particularly at the growth plates around the knee, which can cause severe bone pain. In addition to hypophosphatemia and a decreased tubular reabsorptive threshold for phosphate, untreated patients with XLH have normal serum levels of calcium, normal-to-high parathyroid hormone (PTH) levels, elevated (or sometimes normal) alkaline phosphatase activity, normal plasma 25-hydroxyvitamin D concentrations, and normal or slightly reduced plasma 1,25-dihydroxyvitamin D concentrations. The defects in bone mineralization consistently respond well to treatment with phosphate and calcitriol, but the effects of this treatment on skeletal growth are highly variable.

Question 520

Mesoblastic nephroma

Answer 520

Congenital mesoblastic nephroma – Congenital mesoblastic nephroma is usually detected within the first year of life or by prenatal ultrasonography and can be divided into the classic and cellular subtypes. It has been associated with hypertension and elevated concentrations of calcium and renin. Mesoblastic nephroma is the most common congenital renal neoplasm. It is a solitary hamartoma, and it is usually benign and unilateral. Sonograms show mesoblastic nephroma as a complex mass that may contain cystic areas. Mesoblastic nephroma is the primary consideration in a neonate with a solid renal mass.

Question 521

What percentage of children with Trisomy 21 and transient myeloproliferative disorder will go on to develop leukemia?

Answer 521

25% answer in exam. | 30% seen elsewhere.

Question 522

HSP/IgAV ddx

Answer 522

There are a number of causes of small vessel vasculitis (including IgAV) that may present with asymmetric polyneuropathy, palpable purpura, and/or pulmonary or kidney involvement. These diseases include primary vasculitides (eg, granulomatosis with polyangiitis), microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome), and vascular inflammation secondary to a connective tissue disorder (eg, systemic lupus erythematosus [SLE]) or to an infectious disease (eg, hepatitis B or C). In general, these diseases are uncommon in children. No laboratory test is diagnostic for IgAV. However, confirmation of a normal platelet count and coagulation studies (prothrombin time [PT], partial thromboplastin time [PTT], and bleeding time) are necessary when clinical features do not allow conclusive distinction of IgAV from other diseases that present with purpura due to thrombocytopenia or coagulopathy. Laboratory evaluation of autoantibodies, including antinuclear antibodies, anti-double-stranded DNA (anti-dsDNA), and antineutrophil cytoplasmic antibodies (ANCAs), is typically negative in IgAV. Abnormal results for any of these studies may differentiate IgAV from the other causes of small vessel vasculitis. The majority of patients have normal complement levels, but hypocomplementemia has been reported both in IgAV and in AHEI.

Question 523

ANCA types/associations

Answer 523

cANCA/PR3 antibodies are most frequently seen in granulomatosis with polyangiitis and pANCA/ MPO antibodies are most often associated with microscopic polyangiitis. However, both may be seen in all three types with varying degrees of reactivity.

Question 524

PBB

Answer 524

PBB is one of the most common causes of chronic wet cough, particularly in young children (<5 years of age), accounting for approximately 40 percent of referrals to pediatric pulmonary specialist clinics in resource-rich countries. Diagnosis — PBB is usually diagnosed based on clinical criteria (termed "clinically-based PBB"): ●Chronic wet cough (duration at least four weeks) ●No other symptoms or signs of other causes ●No evidence of an alternative diagnosis after a standard evaluation (including normal spirometry and normal radiograph, other than bilateral peribronchial accentuation) ●Resolution of the cough after a two-week course of appropriate antibiotics Most commonly due to non-typable Haemophilis. Also strep pneumo and Moraxella catarrhalis. Treatment — Children with a clinical diagnosis of PBB should be treated with a prolonged course of antibiotics, with a minimum course of two weeks, e.g. augmentin.

Question 525

Social communication disorder

Answer 525

A. Persistent difficulties in the social use of verbal and nonverbal communication as manifested by all of the following: 1. Deficits in using communication for social purposes, such as greeting and sharing information, in a manner that is appropriate for the social context. 2. Impairment of the ability to change communication to match context or the needs of the listener, such as speaking differently in a classroom than on a playground, talking differently to a child than to an adult, and avoiding use of overly formal language. 3. Difficulties following rules for conversation and storytelling, such as taking turns in conversation, rephrasing when misunderstood, and knowing how to use verbal and nonverbal signals to regulate interaction. 4. Difficulties understanding wliat is not explicitly stated (e.g., making inferences) and nonliteral or ambiguous meanings of language (e.g., idioms, humor, metaphors, multiple meanings that depend on the context for interpretation). B - functional impairement. C - onset in early developmental period D - not better explained, e.g. autism.

Question 526

Difference autism and social communication disorder

Answer 526

Restricted/repetitive behaviours. DSMV: Autism spectrum disorder is the primary diagnostic consideration for individuals presenting with social communication deficits. The two disorders can be differentiated by the presence in autism spectrum disorder of restricted/repetitive patterns of behavior, interests, or activities and their absence in social (pragmatic) communication disorder.

Question 527

Mobitz 1 vs 2

Answer 527

Mobitz 1 - exhaustion, PR lengthens until one is missed. Mobitz 2 - random, regular PR then one isn't conducted. Mobitz 2 worse, more likely to progress to complete heart block.

Question 528

Which cells produce Anti-Mullerian Hormone?

Answer 528

Sertoli cells. Internal urogenital tract — The internal urogenital tracts arise from initially nonbinary sexually indifferent gonads and two sets of ducts, the wolffian and müllerian ducts, which are present in early embryos regardless of chromosomal sex. ●In typical females, the gonads develop into ovaries; the müllerian ducts give rise to the fallopian tubes, uterus, and upper vagina, and the wolffian ducts persist in vestigial form. ●In typical males, the gonads develop into testes; the wolffian ducts give rise to the epididymides, vasa deferentia, seminal vesicles, and ejaculatory ducts, and the müllerian ducts regress. AMH, a glycoprotein formed by Sertoli cells of the fetal testis beginning at approximately six weeks of development, causes regression of the müllerian ducts.

Question 529

ADHD most common comorbidity

Answer 529

ODD

Question 530

Oculogyric crisis antidote

Answer 530

Benztropine Oculogyric crisis is a dystonia.

Question 531

Which test measures total lung capacity?

Answer 531

Plethysmography

Question 532

The most common cause of errors when taking a blood pressure is...

Answer 532

Incorrect cuff size

Question 533

Hereditary angioedema

Answer 533

Generally due to deficient/dysfunctional C1 esterase inhibitor. Type 1 = deficient AND dysfunctional. Type 2 = dysfunctional only. Both cause low C4. Hereditary angioedema (HAE) is a disease characterized by recurrent episodes of angioedema, without urticaria (also called wheals) or pruritus, which most often affect the skin or mucosal tissues of the upper respiratory and gastrointestinal tracts. Although the swelling is self-limited and resolves in two to five days without treatment, laryngeal involvement may cause fatal asphyxiation. HAE with C1 inhibitor deficiency/dysfunction — HAE type I is due to C1-INH deficiency, and type II is caused by C1-INH dysfunction. Together, these two disorders are called HAE with C1-INH deficiency. HAE type I accounts for 85 percent of HAE-C1-INH kindreds and is characterized by reduced secretion of the C1-INH protein. Upon testing, plasma protein (antigenic) and functional C1-INH levels are both low. HAE type II results from the presence of a dysfunctional C1-INH protein, which is present in normal or elevated amounts. Upon testing, C1-INH function is low, but protein levels are normal or elevated. C1-INH deficiency or dysfunction results in low levels of complement component 4 (C4) because the C1 complex normally cleaves C4 as part of the classical complement pathway, and this is exaggerated if C1-INH is deficient.

Question 534

Incubation period definition

Answer 534

The period between exposure to an infection and the appearance of the first symptoms.

Question 535

Transport maximum

Answer 535

Exam Q: What is the term for the point of maximal absorption of a solute by the renal tubule? For most substances actively re-absorbed or secreted in the kidney, there is a transport maximum. In physiology, transport maximum (alternatively Tm or Tmax) refers to the point at which increase in concentration of a substance does not result in an increase in movement of a substance across a cell membrane.

Question 536

Exam finding XLA

Answer 536

There is only one characteristic physical finding of XLA and that is the absence or near absence of the B cell-rich tonsils and adenoids. Recurrent bacterial respiratory tract infections are the most common manifestation of XLA. The infections are usually caused by encapsulated pyogenic bacteria, organisms for which opsonization by antibody is a primary host defense.

Question 537

Diagnosis XLA

Answer 537

Prev exam Q - newborn with fam hx, what test to diagnose? ?Lymphocyte subsets - 20% of patients with XLA don't have a BTK mutation... A definitive diagnosis is made when a male patient has hypogammaglobulinemia or agammaglobulinemia, <2 percent CD19+ B cells, and either a male family member of maternal lineage who is documented to also have agammaglobulinemia and <2 percent CD19+ B cells or a confirmed (by DNA, messenger RNA [mRNA], or protein analysis) defect in the BTK gene or Btk expression.

Question 538

What is the mechanism of oseltamivir?

Answer 538

Inhibit viral neuraminidase from allowing exit from the cell. UTD: Neuraminidase inhibitors prevent the release of virions from the host cell. Neuraminidase inhibitors are active against influenza A viruses and influenza B viruses. Then lists Oseltamivir...

Question 539

Neopterin

Answer 539

Prev Q: Which CSF metabolite is the most sensitive marker of inflammation? Neopterin is regarded as a valuable early biochemical marker of the cellular immune response during inflammation... Therefore, CSF neopterin serves as a strong inflammatory biomarker for practitioners.

Question 540

Pyrin inflammasomopathies

Answer 540

FMF Hyper IgD syndrome PAPA (The syndrome of pyogenic arthritis, pyoderma gangrenosum, and acne) Pyrin-associated autoinflammation with neutrophilic dermatosis Periodic fever, immunodeficiency, and thrombocytopenia

Question 541

Cryopyrin inflammasomopathies

Answer 541

Cryopyrin-associated periodic syndromes: Familial cold autoinflammatory syndrome, Muckle-Wells syndrome, Neonatal-onset multisystem inflammatory disorder. Majeed syndrome

Question 542

Function hippocampus

Answer 542

Right hippocampus plays a critical role in spatial memory in older adults, while the role of left hippocampus in verbal memory is more prominent.

Question 543

Intellectual disability cut offs (mild, mod, etc)

Answer 543

mild ID IQ 50-55 to 70 55 to 70 moderate ID IQ 35-40 to 50-55 severe ID IQ 20-25 to 35-40 profound ID IQ below 20-25

Question 544

What anti-epileptic drug demonstrates irreversible inhibition of GABA transaminase?

Answer 544

Vigabatrin

Question 545

Dysferlin

Answer 545

Dysferlinopathies encompass pathogenic variants in the dysferlin gene (DYSF) that cause two main types of muscular dystrophy, LGMD (limb girdle muscular dystrophy) R2 and Miyoshi distal myopathy, and other muscle disorders with variable phenotypes ranging from asymptomatic hyperCKemia to severe disability. The DYSF gene provides instructions for making a protein called dysferlin. This protein is found in the thin membrane called the sarcolemma that surrounds muscle fibers. Dysferlin is thought to aid in repairing the sarcolemma when it becomes damaged or torn due to muscle strain.

Question 546

Hypoxia with normal A-a gradient

Answer 546

Hypoventilation If the A-a gradient is normal, then the cause of hypoxia is low oxygen content in the alveoli, either due to low O2 content in the air (low FiO2, as in the high altitude) or more commonly due to hypoventilation like the central nervous system (CNS) depression, OHS, or obstructed airways as in COPD exacerbation.

Question 547

Cause of McCune Albright Syndrome

Answer 547

McCune-Albright syndrome is a rare mosaic disorder caused by postzygotic activating mutations of the GNAS1 gene, encoding the alpha subunit of the stimulatory G protein. Patients with MAS have a somatic (postzygotic) mutation of the alpha subunit of GNAS, which encodes the Gs protein that activates adenylyl cyclase.

Question 548

Neuromyelitis optica spectrum

Answer 548

Neuromyelitis optica spectrum disorders (NMOSD; previously known as Devic disease or neuromyelitis optica [NMO]) are inflammatory disorders of the central nervous system characterized by severe, immune-mediated demyelination and axonal damage predominantly targeting optic nerves and the spinal cord. Unlike multiple sclerosis, necrosis and cavitation typically involve both gray and white matter. The pathophysiology of NMOSD is thought to be primarily mediated by the humoral immune system. The most important of these was the identification of a NMOSD disease-specific autoantibody, initially termed the NMO-immunoglobulin G (IgG) antibody, and now referred to as the AQP4 autoantibody. Hallmark features of NMOSD include acute attacks of bilateral or rapidly sequential optic neuritis (leading to severe visual loss) or transverse myelitis (often causing limb weakness, sensory loss, and bladder dysfunction) with a typically relapsing course. Attacks most often occur over days, with variable degrees of recovery over weeks to months.

Question 549

Infant mortality

Answer 549

The infant mortality rate is defined as the number of deaths of children under one year of age, expressed per 1 000 live births.

Question 550

How do glucocorticoids cause osteoporosis

Answer 550

Google: Glucocorticoids cause profound effects on bone cell replication, differentiation, and function. Glucocorticoids increase bone resorption by stimulating osteoclastogenesis by increasing the expression of RANK ligand and decreasing the expression of its decoy receptor, osteoprotegerin. UTD: Essentially short term increased osteoclast activity as above, longer term more d/t reduced osteoblast activity. With long-term use, the predominant effect of glucocorticoids on the skeleton is reduced bone formation.

Question 551

Prevent selection bias

Answer 551

Randomisation

Question 552

Ascertainment/sampling bias

Answer 552

In statistics, sampling bias is a bias in which a sample is collected in such a way that some members of the intended population have a lower or higher sampling probability than others. It results in a biased sample of a population in which all individuals, or instances, were not equally likely to have been selected. Appropriate inclusion of cases and controls within case-control studies is essential to avoid ascertainment bias. In cohort studies, knowledge of exposures of interest should be kept separate from screening, identification and recording of relevant outcomes of interest.

Question 553

Detection bias

Answer 553

Detection bias refers to systematic differences between groups in how outcomes are determined. Blinding (or masking) of outcome assessors may reduce the risk that knowledge of which intervention was received, rather than the intervention itself, affects outcome measurement.

Question 554

Measurement bias

Answer 554

Measurement bias is a systematic distortion of the results of treatment comparisons that can occur when people measuring outcomes - whether researchers, healthcare providers, or study participants - are aware of the treatment allocation when they are measuring outcomes. Prevent with blinding of treatment allocation.

Question 555

SPINK1

Answer 555

Hereditary pancreatitis The SPINK1 gene encodes a pancreatic secretory trypsin inhibitor that is regulated as an acute phase reactant. SPINK1 mutations can cause familial pancreatitis with an autosomal recessive pattern in families in which both parents have a mutation.

Question 556

PCOS and COCP

Answer 556

Exam Q 2021 - Increases sex hormone binding globulin. Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). COCs, which contain estrogen and progestin, usually are the first-line treatment for adolescents with PCOS and abnormal menstrual bleeding or cutaneous signs of androgen excess. The estrogen-progestin combination suppresses the hypothalamic-pituitary-ovarian axis and reduces excess androgen production by the ovary, which improves menstrual regularity and decreases anovulatory uterine bleeding, hirsutism, and acne. The progestin component also inhibits endometrial proliferation, preventing hyperplasia and the associated risk of carcinoma.

Question 557

GSD1 - enzyme deficiency

Answer 557

Glucose-6-phosphatase deficiency, also known as von Gierke disease, is a glycogen storage disease (GSD). It was the first GSD to have the responsible enzyme defect identified and therefore is designated GSD I. The defective enzymes involved in GSD I are mainly active in the liver and kidney. Patients present with manifestations related to hypoglycemia around three to four months of age. The diagnosis is confirmed by genetic testing. Treatment is focused on maintenance of physiologic glucose levels.

Question 558

Factor V Leidin

Answer 558

Activated protein C resistance - there are other forms but FVL is the most common. Factor V Leiden (FVL) results from a point mutation in the F5 gene, which encodes the factor V protein in the coagulation cascade. FVL renders factor V (both the activated and inactive forms) insensitive to the actions of activated protein C (aPC), a natural anticoagulant.

Question 559

PMP-22

Answer 559

CMT-1A. CMT1A is associated with a 1.5 Mb duplication or, less commonly, a single nucleotide variant of the peripheral myelin protein 22 (PMP22) gene on chromosome 17p11.2-p1.

Question 560

Hypocretin

Answer 560

Narcolepsy type 1, previously called narcolepsy with cataplexy, includes cataplexy as one of the earliest symptoms and is associated with low cerebrospinal fluid (CSF) orexin (also called hypocretin) levels.

Question 561

WPW and verapamil

Answer 561

Contraindicated. Verapamil may result in significant acceleration of ventricular response during atrial fibrillation in the Wolff-Parkinson-White syndrome.

Question 562

Mechanism of influenza pandemics

Answer 562

Influenza viruses constantly change through a process called antigenic drift. This is the random accumulation of mutations in the haemagglutinin (HA), and to a lesser extent neuraminidase (NA) genes, recognized by the immune system. It is most pronounced in influenza A viruses.

Question 563

Physiologic characteristics of REM sleep

Answer 563

Prev exam Q. Reduced muscle tone. Increased variability HR/RR. As we progress from wakefulness through the stages of non-REM sleep, our breathing rate slightly decreases and becomes very regular. During REM sleep, the pattern becomes much more variable again, with an overall increase in breathing rate. As compared to wakefulness, during non-REM sleep there is an overall reduction in heart rate and blood pressure. During REM sleep, however, there is a more pronounced variation in cardiovascular activity, with overall increases in blood pressure and heart rate. With REM sleep, changes occur in brain signaling which cause reduced muscle tone in many of the body's muscles; this may be called REM sleep muscle paralysis or muscle atonia. This is considered a normal function of REM sleep.

Question 564

Most common ophthalmological lesion in a child with rubella?

Answer 564

Cataracts. Cataracts occur in approximately one-quarter of infants with CRS.

Question 565

Small blue round cell tumours

Answer 565

Tumors that belong to this group are: ``` Desmoplastic small-round-cell tumour Ewing's Sarcoma/PNET Neuroblastoma Medulloblastoma Rhabdomyosarcoma Synovial sarcoma Carcinoid tumor Mesothelioma Small cell lung cancer Wilms' tumour Retinoblastoma Small-cell lymphoma Hepatoblastoma - only the anaplastic form has round blue cells, the more common fetal and embryonal types do not Merkel cell carcinoma Mesenchymal chondrosarcoma ```

Question 566

FLNB gene mutation disorders

Answer 566

Larsen syndrome Boomerang dysplasia Spondylocarpotarsal syndrome

Question 567

Which of the following is the most helpful tool to determine if the result is clinically significant?

Answer 567

Effect size. Correct. Effect size is a measure of the size of the effect (or difference between the two. Is 15 mins really a clinically significant effect?). Other factors to consider would be the side effect profile of the new drug, the cost, ease of administration etc.

Question 568

Pearson syndrome

Answer 568

Pearson syndrome is caused by mitochondrial DNA deletions and is usually fatal in infancy. The mutations lead to sideroblastic anaemia, neutropaenia, thrombocytopaenia and pancreatic dysfunction.

Question 569

TLS treatment options/components

Answer 569

Hyperhydration (2-3L/m^2/day) Bicarb/alkalinisation Allopurinol Rasburicase Furosemide no role (as per learnmed).

Question 570

UC extraintestinal manifestations

Answer 570

As per learnmed: Fever and arthritis are the most common extra-intestinal manifestations, other manifestations include erythema nodosum, pyoderma gangrenoum, and primary sclerosing cholangitis.

Question 571

What is most predictive of a child suspected to develop congenital myotonic dystrophy (CDM1)?

Answer 571

Methylation patterns flanking the CTG repeat. Learnmed question. Myotonic dystrophy is an autosomal dominant condition with variable penetrance and complex genetics. It is considered a triplet repeat disorder of the DM1 gene (dystrophia myotonica). Yet typically, it is the mother who transmits the disease, and children born of affected mothers are more severely affected than those born of affected fathers. The reason for this comes from protein kinase methylation patterns flanking the CTG repeat. These methylation patterns are stronger indicators of CDM1 than repeat size. Barbe, L et al (2017) CpG Methylation, a Parent-of-Origin Effect for Maternal-Biased transmission of Congenital Myotonic Dystrophy. Am. J. Hum. Genet, 100, 488-505. Myotonic dystrophy (DM) mutations with trinucleotide CTG repeats <50 are typically normal, 50-99 may exhibit cataracts, while those with repeats beyond 100 will present with myotonia and weakness. Myotonia may be absent in the neonatal period. "There is no evidence that mutations in mtDNA are involved in the pathogenesis of congenital myotonic dystrophy" [Poulton, J et al (1995) Mitochondrial DNA does not appear to influence.... J. Med. Genet, 32, 732-735] Clinically, methylation patterns may not yet be available for pathology testing, unlike CTG repeat testing. The correct answer is A. If option A was not provided, then the answer would be B (CTG repeat size).

Question 572

PNH diagnosis

Answer 572

Bone marrow flow cytometry. Previously acid serum lysis test. A. A test previously used to diagnose paroxysmal noturnal haemoglobinuria. Detects the sensitivity of PNH red cells to lysis by complement. Complement is activated by the reduction of the pH of fresh serum to 6.4. Haemolysis of red cells indicated a positive test. PNH is a disorder characterized by an increased sensitivity of cells to the action of complement due to an absence of GPI linked proteins sue to an abnormality in the PIG-A gene, which causes a defect in the glycosyl-phosphatidyl-inositol anchor (GPI). B. Now used to diagnose PNH by detecting the absence of GPI linked proteins from the surface of PNH haematopoietic cells.

Question 573

Griscelli syndrome

Answer 573

Griscelli syndrome is a rare, autosomal-recessive disorder caused by a mutation in the intracellular trafficking genes which leads to partial oculocutaneous albinism and immunodeficiency. Hair shaft findings are pathognomic. Learnmed stem: A child presents with partial oculocutaneous albinism presents with recurrent infections. On examination of the hair shaft, large, irregular clumps of melanin granules are distributed near the medulla of the hair shaft. The shaft appears uniformly white under polarised light microscopy. Blood film is normal. Which of the following is the most likely diagnosis?

Question 574

Salter Harris fracture management

Answer 574

1 and 2 can be managed with closed reduction. 3 and above need open reduction - risk to growth plate. 2, 3, 4 = M E spells ME 2 = metaphysis 3 = epiphysis 4 = both ``` 1 = through physis 5 = crush ``` 3/4/5 may affect growth

Question 575

The most important known factor which influences the rate of development of microvascular complications in patients with diabetes is...

Answer 575

Hyperglycaemia. Risk is related to duration, but RATE relates to degree of hyperglycaemia.

Question 576

Tay Sachs vs Niemann Pick A boy develops progressive weakness from the age of four months. He was previously able to sit without support but has lost this skill. On examination, he is macrocephalic and hyperreflexic. Fundoscopy reveals a cherry red macula.

Answer 576

Tay Sachs disease is a lysosomal storage disorder that presents after 3 months with regression of gross motor skills. Macrocephaly is common because of accumulation of GM2 ganglioside in the brain. Niemann Pick Disease Type A is also associated with developmental regression and a cherry red macula but reflexes are absent or reduced. Macrocephaly is not a usual feature.

Question 577

Hunter, Hurler, Morquio A child presents at six months with developmental delay and recurrent sinopulmonary infections. On examination, the child has hepatosplenomegaly and corneal clouding.

Answer 577

Correct answer: Hurlers syndrome Explanation: Hunters, Hurlers and Morquio syndrome are all mucopolysaccharidoses. Hunters syndrome is not associated with corneal clouding (think of the Hunter needing good eyesight!) Morquio syndrome is characterised by predominantly skeletal problems and although corneal clouding can occur, it is far more common in Hurlers syndrome. Children with Hurlers syndrome may present with recurrent sinopulmonary infections and developmental delay before the characteristic facial features have developed.

Question 578

Recombinase activating gene 1 defect and recombinase activating gene 2 defect (RAG1 and 2)

Answer 578

Omenn syndrome Omenn syndrome is a variant of SCID (severe combined immunodeficiency). Children present with recurrent infections, exudative erythroderma, lymphadenopathy, hepatosplenomegaly, chronic persistent diarrhoea, and failure to thrive.

Question 579

Signs suggestive of forced sexual penetrations

Answer 579

Learnmed: - Extensive bruising on the hymen - Laceration (tear, partial or complete) of the hymen (acute) - Perianal lacerations extending deep to the external anal sphincter (Not to be confused with partial failure of midline fusion.) - Hymenal transection (healed): An area between 4 o'clock and 8 o'clock on the rim of the hymen, where it appears to have been torn through, to or nearly to the base, so there appears to be virtually no hymenal tissue remaining at that location. - Missing segment of hymenal tissue. Area in the posterior (inferior) half of the hymen, wider than a transection, with an absence of hymenal tissue extending to the base of the hymen, which is confirmed using additional positions or methods.

Question 580

Attrition bias

Answer 580

Attrition bias describes the bias that occurs when people who are lost to follow up. This may occur because participants do not continue treatment or are no longer willing or able to participate in the study.

Question 581

Methicillin Resistant Staphylococcus Aureus (MRSA) is a major health concern worldwide, and is increasingly implicated in nosocomial infections. Resistance is frequently mediated by bacterial acquisition of the mecA gene, resulting in:

Answer 581

Alteration of penicillin binding protein Beta-lactams need to bind to Penicillin-Binding Proteins (PBPs) in order to disrupt cell wall synthesis and induce cell death. Methicillin is a semi synthetic penicillin which is stable against staphylococcal penicillinase. The mechanism for resistance to methicillin in staphylococcal species is thus through the acquisition of the mecA gene, which codes for PBP2a, a PBP which has low affinity to penicillins, cephalosporins and carbapenems.

Question 582

Timothy syndrome

Answer 582

There are rare reports of infants with severe LQTS and syndactyly involving both fingers and toes, frequently with associated patent ductus arteriosus and other cardiac abnormalities. The constellation of QT prolongation (usually marked), syndactyly, and often developmental delays is called Timothy syndrome. High association with autism (70%).

Question 583

The resistant organisms are sometimes remembered as the ESKAPE organisms. These include...

Answer 583

``` Enterococcus faecium (vancomycin) Staph aureus (methicillin and vancomycin) Klebsiella pneumoniae (ESBL or carbapenems) Acinetobacter baumannii (carbapenems) Pseudomonas aeruginosa (carbapenems) Enterobacter species (cephalosporins) ```

Question 584

What cardiac structure is most likely to be affected in chronic rheumatic heart disease?

Answer 584

Mitral, then aortic (or combined), then tricuspid. It's in the name! rheuMATic.

Question 585

Markers of disease activity SLE

Answer 585

dsDNA | C3/C4/CH50

Question 586

CHD7

Answer 586

CHARGE syndrome

Question 587

PAX2 gene

Answer 587

Renal coloboma syndrome Renal-coloboma syndrome is associated with mutations in the PAX2 gene. It is an autosomal disorder associated with coloboma, renal abnormalities, SNHL, seizures and joint laxity. Marfan syndrome is associated with joint laxity and ocular abnormalities – specifically ectopia lentis – but is not usually associated with renal abnormalities.

Question 588

Metanephros

Answer 588

Embryological structure. | Becomes the kidney.

Question 589

Glucokinase

Answer 589

Glucokinase is an enzyme that facilitates phophorylation of glucose to glucose-6-phosphate. It occurs in cells in the liver, pancreas, gut, and brain.

Question 590

Tocilizumab

Answer 590

Tocilizumab is a recombinant humanized anti-human monoclonal antibody directed against the IL 6 receptor which is used in the treatment of systemic onset JIA and polyarticular JIA. It is given by infusion.

Question 591

Etanercept

Answer 591

Etanercept is a biologic tumor necrosis factor (TNF) inhibitor; the drug acts as a soluble TNF receptor and binds TNF-alpha and TNF-beta.

Question 592

Anakinra

Answer 592

Anakinra is an IL1 inhibitor used in the treatment of systemic JIA. Canakinumab is also an IL1 inhibitor but is administered monthly. Rilonacept is another Il1 inhibitor used in the treatment of systemic JIA but it is administered weekly. All are subcutaneous injections.

Question 593

Bleomycin

Answer 593

G2 | Bleomycin is a cell-cycle specific glycopeptide antibiotic that arrests rapidly dividing cells at the early G2 stage.

Question 594

Cytarabine

Answer 594

S Cytarabine is a cell-cycle specific pyrimidine analogue that inhibits DNA polymerase leading to arrest of DNA synthesis at the S stage.

Question 595

Asparaginase

Answer 595

G1 Asparaginase is a cell-cycle specific enzyme that depletes leukemic cells of asparagine thereby arresting growth at the G1 stage.

Question 596

Vincristine

Answer 596

Vinca alkaloid | Mitosis phase of cell cycle

Question 597

Cell cycle independent chemotherapeutics

Answer 597

``` Platinating agents (cisplatin, carboplatin) Alkylating agents (cyclophosphamide, busulphan) ```

Question 598

Etoposide cell cycle

Answer 598

Etoposide is cell cycle dependent and phase specific, affecting mainly the S and G2 phases.

Question 599

Ganciclovir

Answer 599

Ganciclovir, and inhibitor of viral DNA polymerase, is the most extensively studied antiviral for symptomatic congenital CMV infection. It has been demonstrated to prevent deterioration of hearing impairment. Neutropenia is a common side effect. It is only able to be administered IV; valganciclovir is an oral prodrug which is an alternative treatment option, but has been less extensively researched.

Question 600

pre-exposure prophylaxis (PrEP)

Answer 600

Tenofovir disoproxil and emtricitabine (Truvada) is the only PBS listed medication for PrEP. If taken correctly it is 99% effective at preventing HIV transmission. It should be considered in those at risk of HIV (e.g. men who have sex with men (MSM) who have a sexual partner with HIV and a detectable viral load, men or women who have casual anal sex without condoms with MSM, or a woman whose partner is HIV positive and is planning natural conception). It is recommended to complete HIV and STI testing, as well as assess renal function, prior to prescribing PrEP and at three month intervals whilst taking PrEP, and to also provide information regarding safe sex.

Question 601

Causes neonatal seizures

Answer 601

In decreasing order of frequency: HIE (46%) > stroke (13%) > ICH (11%) > unknown > infection > electrolyte disturbance > genetic epilepsy > CNS malformation = IEM

Question 602

Dent disease

Answer 602

Dent disease is also known as X-linked recessive nephrolithiasis. Children with Dent disease present with polyuria, microscopic haematuria, proteinuria or kidney stones. 75% of patients develop kidney stones. Most cases of Dent disease are caused by mutations in the CLCN5 gene that inactivates a voltage-gated chloride transporter named CLC-5. Some cases are associated with mutations in the OCRL1 gene, which is also the gene mutation associated with Lowe oculocerebrorenal syndrome.

Question 603

CLCN5

Answer 603

Dent disease

Question 604

GABRA1

Answer 604

Juvenile myoclonic epilepsy

Question 605

PRRT2

Answer 605

Self-limiting and familial infantile seizures