Metabolics/Genetics Flashcards
1
Q
Classic presentation for galactosemia
A
- Jaundice, hepatomegaly
- FTT, poor feeding, emesis
- Sepsis (E. coli)
- Cataracts
2
Q
Inheritance pattern for Marfan Syndrome
A
Autosomal dominant
3
Q
Features of Noonan Syndrome
A
- Dysmorphic features = low posterior hairline, wide philtrum, hypertelorism, down slanting palpebral fissures, short nose with bulbous tip, cubitus valgus, nuchal skin fold, wide bi-temporal distance
- Cardiac = R sided lesions (PV stenosis, double outlet RV, HCM), lymphedema
- CNS = seizures, chiari I malformation, mild ID, eye issues
- Other = endo (short stature, hypothyroidism), MSK (scoliosis, club foot, pectus abnormality), GU (renal anomalies), heme (thrombocytopenia), onc (JMML)
4
Q
Williams Syndrome - cardiac manifestations
A
Supravalvular AS + PS
Pulmonary valve stenosis
Hypertension
5
Q
Sturge-Weber Syndrome - derm manifestations
A
Port wine stain V1/V2
6
Q
What genetic syndrome do you think for hemihypertrophy?
A
BW
7
Q
What neoplasm to look for for BW?
A
Hepatoblastoma
Wilm’s tumor
8
Q
What oncology screening for BW?
A
Abdo US q3m
AFP q3m
Until age 8
9
Q
Electrolyte disturbance in CAH?
A
Hypoglycaemia
Hyponatremia
Hyperkalemia
10
Q
What neuro complication in achondroplasia?
A
Risk of foremen magnum narrowing/stenosis that can lead to hydrocephalus and OSA
11
Q
SMA - genetic inheritance
A
Autosomal recessive
12
Q
5 BM failure congenital syndromes
A
Fanconi anemia Schwachmann Diamond Dyskeratosis congenita Pearson syndromes Congenital amegakaryocytic thrombocytopenia
13
Q
What BM failure syndrome is associated with VACTERL?
A
Fanconi anemia
14
Q
What BM syndrome is associated with hair/skin findings?
A
Dyskeratosis congenita
15
Q
Non-ketotic hypoglycaemia (x3 causes)
A
GDM/SGA/prep
Insulin mediated = hyperinsulinemia
Lipid disorders = beta oxidation, carnitine
16
Q
VLCAD complications (x2)
A
Rhabo
Cardiomyopathy
17
Q
Hemophilia A inheritance pattern
A
X-linked recessive
18
Q
Most common chromosomal abnormality involved spontaneous first trimester miscarriages?
A
Trisomy 16
19
Q
Turner Syndrome - karyotype
A
45 XO
20
Q
Turner Syndrome - clinical presentation
A
- Dysmorphic ftrs: Low posterior hairline, cubitus valgus, nuchal skin fold, abnormal ears, shield chest with wide-spaced nipples, short 4th metacarpal, hyperconvex nails
- CVS: BAV, coarct, AS, HTN, lymphedema
- CNS: IQ normal, SNHL + CHL hearing loss, strabismus
- Endo: met syndrome, hypothyroid, short stature
- MSK/derm: pigment nevi, scoliosis, DDH, cystic hygroma
- Onc: neuroblastoma, gonadoblastoma
- Gyne: Ovarian failure
- GU: renal anomalies (horseshoe kidney, solitary kidney)
21
Q
Friedrich Ataxia - inheritance pattern, pathophys of chromosomal abnormality, and x3 classical clinical features
A
- Auto recessive
- Chromo 9q13 = frataxin protein –> deficiency leads to accumulation of iron in mitochrondria = oxidative stress
- Features: ataxic gait, extensor plantar responses, loss of DTRs
22
Q
Most likely finding on blood gas for urea cycle defect
A
Respiratory alkalosis
23
Q
x3 top findings on labs for urea cycle defect
A
- resp alkalosis
- hyperammonemia
- little/no urea
24
Q
Inheritance pattern for OTC deficiency
A
X-linked recessive
25
What IEM presents with more significant ketosis?
Organic acidemias
26
Important severe, complications from organic acidemias?
Strokes, myocarditis, pancreatitis
27
IEM cause for subdural hematoma and on ddx for maltreatment
Glutaric acidemia
28
IEM diagnosis on ddx for Marfan Syndrome
Homocysteinuria
29
x2 dx to think of for neonates with ketonuria
Organic acidemias and maple syrup urine disease
30
IEM presenting with liver failure, conjugated hyperbili, and RTA (type II)
Tyrosinemia
31
IEM with neutropenia
GSD 1
32
IEM to think of for rhabdo out of in keeping of mechanism
GSD-5 = McArdle
33
When can you get a false positive galactosemia screen?
G6PD
34
Medical based reason for soy based formula (x1)
Galactosemia
35
FAOD labs (x2)
- Hepatitis
| - Non-ketotic hypoglycemia
36
Peroxismal disorder presenting in neonates
Zellweger
37
What is the dx that has developmental regression (starting within school aged), new spasticity, and adrenal failure?
Adrenoleukodystrophy
38
MELAS - what does that stand for?
Mitochondrial encephalomyopathy lactic acidosis, stroke like episodes
39
Sturge Weber - inheritance
Sporadic
40
Sturge Weber - derm and classic CNS sign
- Angioma involving leptomeninges - vascular lesion, tram track sign
- V1 and V2 port wine stain
41
Lesch Nyhan Syndrome - inheritance
X linked recessive
42
IEM with gout, kidney stones, dev delay, self injurious behav
Lesch Nyhan Syndrome
43
What x2 genotypes has the worst disease for alpha 1 antitrypsin?
SZ and ZZ
44
Incontinentia pigmenti - inheritance, derm manifestation, dental
- X linked dominant (males die in utero)
- Stages: 1 vesicles (linear/whorls), 2 ketatotic plaques, 3 hypopigmentation, 4 hyperpigmentation
- Peg teeth
45
What tumor is classic for Denys-Drash?
Wilm’s tumor
46
Triad of Denys Drasch
Nephropathy, ambiguous genitalia, Wilm’s tumor
47
IEM presenting with learning disabilities and behaviour problems that is often dx with ADHD
X linked leukodystrophy
48
Sacral agenesis - associated with?
IDM
49
Trinucleotide repeat disorders (4)
Fragile X, myotonic dystrophy, spinocerebellar ataxia, Huntington’s disease
50
PHACE Syndrome/association
- Posterior fossa abnormalities - dandy walker malformation
- hemangioma
- arterial/aortic abnormality
- cardiac
- eye abnormality
- sternal abnormalities
51
Supravalvular aortic stenosis
William Syndrome
52
CATCH-22
For DiGeorge Syndrome:
- Cardiac
- AbN facies
- Thymic hypoplasia
- Cleft lip+palate
- HypoCa
53
Inheritance pattern for DiGeorge
Autosomal dominant
54
What is the most common genetic condition associated with cutis aplasia?
T13
55
What is a clue on ECG for T21 that suggests AVSD?
Left axis deviation
56
What cardiac lesions are Turner syndrome patients at risk for?
Coarctation, BAV, long QTc
57
X2 heart lesions in Williams Syndrome
Supravalvular aortic stenosis
| Pulmonary artery stenosis
58
Electrolyte abnormality in Williams Syndrome
HyperCa
59
What eye finding in Williams Syndrome?
Starburst eye pattern
60
What syndrome has aniridia?
WAGR
61
X3 syndromes with Persistent peripheral pulmonary stenosis
Alagille syndrome, noonan, William
62
When should PPS murmur go away?
3-6 months
63
What does Rhizomelic mean?
Proximal aspect of extremity is shorter - example femur
64
Why should we do a CT or MRI around 12 months of age for achondroplasia?
Narrowing of the foremen magnum
65
Differences in homocysteinuria compared to Marfan syndrome?
Higher risk of clotting and decreased cognition
66
Main cardiac abnormality for Noonan Syndrome
Pulmonary stenosis
67
What type of leukaemia for neurofibromatosis type 1?
Juvenile myelomonocytic leukaemia
68
Optho finding in Sturge Weber
Glaucoma
69
What MRI finding for children with Sturge Weber?
Ipsilateral leptomeningeal angioma
70
What neuro manifestation do you worry about for tuberous sclerosis?
Infantile spasms
71
What first line med for infantile spasm in tuberous sclerosis?
Vigabatrin
72
Cardiac rhabdomyosarcoma - what syndrome?
Tuberous sclerosis
73
Ectodermal dysplasia - dental finding
Conal dentition
74
Rett Syndrome - 3 clinical features
Writhing hands, dev regression, seizures
75
Inheritance for Rett Syndrome
MECP2 - X linked dominant
76
What syndrome is good at puzzles?
Prader Willi
77
Onc things to monitor for BW Syndrome?
Hepatoblastoma, Wilm’s tumor
78
Facial asymmetry - syndrome?
Goldenhar syndrome
79
Diagnosis of Cystic Fibrosis
- 1 or more typical features, OR history of CF in sibling, OR abnormal NMS
- PLUS lab evidence: +sweat Cl, x2 known disease causing mutations, abnormal nasal potential difference measurements
80
What syndrome is most likely with seizure disorder, ataxia, absent speech, and microcephaly?
Angelman Syndrome
81
What is the mother at risk for when carrying a baby with DMD?
Cardiomyopathy
82
Inheritance pattern for DMD
X-linked recessive
83
x2 confirmatory tests for DMD
- Muscle biopsy - absent dystrophin, muscle atrophy
| - Genetics - dystrophin gene
84
What mode of inheritance is characterized by male to male transmission?
Autosomal dominant
85
What mode of inheritance is characterized by female only transmission?
X-linked recessive
86
What mode of inheritance is characterized by a horizontal appearance of disease phenotype?
Autosomal recessive
87
What x2 syndromes are associated with Pierre Robin sequence?
- 22q11
| - Stickler Syndrome
88
What syndrome are brushfield spots found in?
T21
89
T21 - facial features?
- Brachycephaly/microcephaly
- Up slanting palpebral fissures
- Epicanthal folds
- Low set ears
- Hearing loss, recurrent AOM
- Flat nasal bridge
90
T21 - MSK features?
- Single palmar crease
- Short 5th digit with clindodactyly
- Short neck with redundant skin
- Wide gap between first two toes
- Hip dysplasia
- Dislocations
- Atlantoaxial instability
91
T21 - GI features?
- Hirschsprung
- Celiac disease
- Duodenal atresia
- TEF
- Imperforate anus
92
Prenatal screen lab findings for T21
- High hCG
| - Low AFP
93
Clinical features of T18
- Rockerbottom feet
- Overlapping fingers
- Clenched fist
- IUGR, microcephaly
- Micrognathia
- Cleft lip/palate
- Hypertonia
- CVS: VSD
94
Clinical features of T13
- Midline defect
- Aplasia cutis congenital
- Microphthalmia, microcephaly
- Hypotonia
- Postaxial polydactyly
- CVS: PDA
95
What syndrome will you see a stellate iris?
William Syndrome
96
Clinical features of William's Syndrome
- Long philtrum (Elfin facies)
- Broad mouth
- Short nose with bulbous tip
- Cocktail personality, anxiety
- Developmental delay
- Joint laxity
97
Classic facial feature of Wolf-Hirschhorn Syndrome?
Greek helmet face
98
BW syndrome malignancies x2
Hepatoblastoma
| Wilms tumor
99
Triad of BW Syndrome
- Omphalocele
- Macroglossia
- Hypoglycemia
100
Ear findings in BW Syndrome
- Ear lobe creases
| - Posterior auricular pits
101
Fragile X - genital feature for F and M
- F = premature ovarian failure
| - M = macroorchidism
102
CVS finding of Fragile X
-MV prolpase
103
Fragile X - what is the trinucleotide repeat?
CGG
104
x2 CVS findings in Turner's
- BAV
| - Coarctation
105
Clinical features of Turner's Syndrome
- Short stature
- Lymphedema
- Shield chest
- Cubitus valgus
- Low posterior hairline
- Posteriorly rotated ears
- Webbed neck
- Short 4th metacarpal bone
- Ovarian dysgenesis
- Horseshoe kidney
- Autoimmune/endo disorders
106
Differentiating clinical features for Turner vs Noonan Syndrome?
-Noonan: down slanting palpebral fissures, intellectual disability, pulmonary stenosis (vs BAV/coarct), normal karyotype
107
What is the most common cause of primary hypogonadism + infertility in males?
Klinefelter Syndrome
108
Karyotype for Klinefelter
XXY
109
Clinical features for Klinefelter
- Gynecomastia
- Tall stature
- Small testes, micropenis
- Infertility
- Intellectual disability, behavioural problems
110
Most effective therapy for Klinefelter Syndrome
Testosterone replacement therapy
111
What x2 malignancies is Klinefelter at risk for?
Breast + testicular cancer
112
Clinical features of Angelman Syndrome
- Jerky ataxic movements (happy puppet)
- Inappropriate bouts of laughter
- Excitable with hand flapping
- Hypotonia
- Seizure
- Microcephaly
- Small/separated teeth
- Fair hair
- Severe intellectual disabilities
- Speech delay
113
Mode of inheritance for Angelman Syndrome
-Maternal UPD
114
What syndrome has almond-shaped eyes?
Prader Willi Syndrome
115
Clinical features of Prader Willi Syndrome?
- Infancy: hypotonia, FTT, feeding problems
- Hyperphagia, central obesity, short stature
- Hypogonadism
- Mild ID, behaviour disorder
- Almond-shaped eyes
116
Mode of inheritance for Prader Willi Syndrome
Paternal UPD
117
Classic finding of Alagille Syndrome
-Paucity of bile ducts
118
Syndrome with nephrogenic DI
Bardet-Biedl
119
Syndrome with LGA, excessive growth during first year of life, large head with frontal prominence, premature tooth eruption, and ventriculomegaly?
Sotos Syndrome
120
Syndrome with trident hands?
Achondroplasia
121
Syndrome with ice cream cone shaped femoral head?
Achondroplasia
122
x2 lab findings in OI
High ALP + hyperCa
123
Cardiac defect in Marfan Syndrome
- Mitral valve prolapse
| - Aortic root dilatation
124
Major criteria for Marfan Syndrome
- Ectopia lentis
- Aortic dilation/dissection
- Family history
125
Clinical features of Treacher Collins Syndrome?
- Zygomatic/mandibular bone hypoplasia
- Eyelid colobomas
- Microretrognathia
- Choanal atresia
- Microtia
- Conductive hearing loss
- Cleft lip + palate
126
Syndrome with facial asymmetry, ear abnormalities, vertebral anomalies, and pathagnomnic limbal dermoid?
Goldenhar Syndrome
127
What clinical features are included in the Pierre Robin sequence?
- Mandibular hypoplasia
- Micrognathia
- Glossoptosis
- U shaped cleft palate
- Upper airway obstruction
128
What syndrome has a white forelock, heterochromia, and skin depigmentation?
Waardenburg Syndrome
129
What GI association is there is Waardenburg Syndrome?
Hirschsprung disease
130
Facial features of Cornelia de Lange?
- Long eyelashes
- Bushing/arched eyebrows
- Hirsutism
- Low hairline
- Down-ward turned mouth
- Thin upper lip
131
What are children with NF1 at risk for?
Malignancies
132
Diagnostic criteria for NF-1
* At least 2 of the following:
- At least 6 CALM (>5mm pre-pubertal; >15mm post-pubertal)
- At least 2 neurofibromas or 1 plexiform neurofibroma
- Axillary/inguinal freckling
- Optic glioma
- At least 2 Lisch nodules (iris hamartoma)
- Distinctive bony lesion: sphenoid dysplasia, tibial pseudoarthrosis, or cortical thickening of the long bone
- First degree relative with NF-1
133
Diagnostic criteria for NF-2
* 1 of the following:
- Bilateral vestibular schwannomas
- Unilateral vestibular schwannoma + first degree relative
- Unilateral vestibular schawannoma OR first degree relative AND any 2 of: meningioma, non-vestibular schwannoma, ependymoma, cataract
134
What is the most common neurological complication in Tuberous Sclerosis?
-Infantile spasms
135
Diagnostic criteria for Tuberous Sclerosis
* MAJOR*
- At least 3 hypomelanotic spots (ash leaf)
- At least 3 angiofibromas
- At least 2 ungual fibromas
- Shagreen patch
- Cortical dysplasia
- Subependymal nodules
- Subependymal giant cell astrocytoma
- Cardiac rhabdomyoma
- Lymhangioleiomyomatosis
- Angiomyolipomas
* MINOR*
- Confetti skin lesions
- Dental enamel pits
- Intra-oral fibromas
- Multiple renal cysts
- Non-renal hamartomas
*Need 2 major OR 1 major/2 minor
136
Classic triad for McCune-Albright Syndrome
- Precocious puberty
- CALM
- Polyostotic fibrous dysplasia
137
Most common presenting sign for precocious puberty in McCune-Albright?
-Vaginal bleeding
138
Most common endo association with McCune-Albright Syndrome?
Hyperthyroidism
139
Major criteria for CHARGE Syndrome (x4)
- Ocular colobomas
- Choanal atresia
- CN dysfunction
- Ear anomalies
140
What syndrome to think about if there is a single umbilical artery?
VACTERL association
141
Clinical features of VACTERL association
- Vertebral defect
- Anal atresia
- CHD (VSD)
- TEF
- Esophageal atresia
- Renal anomalies
- Limb hypoplasia
142
Three categories of protein disorders
- Amino acid disorders
- Organic acid disorders
- Urea cycle disorders
143
Typical presentation for PKU
- No acute signs/symptoms
| - Gradual progression of developmental delay resulting in irreversible profound delays
144
Main method of management for PKU patients
Dietary restriction of phenylalanine
145
Classic presentation of amino acid disorders
- Acute sepsis-like decompensation, liver failure, and/or chronic neurological injury
- Acute symptoms typically occur in a catabolic state that predisposes to protein breakdown (e.g., infection, puberty, procedures)
146
Typical presentation of organic acid disorders in infancy (including symptoms + their cause)
- Feeding intolerance, emesis
- Lethargy
- Non-specific, sepsis-like presentation
- Progression to coma
- Toxin accumulation = metabolic acidosis + hyperammonemia
- Substrate deficiency = production of ketones/lactic acid
147
Acute + chronic management of organic acid disorders
- Acute: stop protein, provide calories, reduce ammonia, IV carnitine
- Chronic: protein restriction + carnitine
148
What is the role of carnitine in organic acid disorders?
- Binds to organic acid + helps to facilitate their excretion
- Leads to carnitine deficiency
149
What acid-base disturbance do organic acid disorders vs urea cycle disorders?
- Organic acid: metabolic acidosis (secondary to build up of acids)
- UCD: respiratory alkalosis (secondary to high ammonia)
150
Typical presentation of urea cycle disorders
- Feeding intolerance, emesis
- Lethargy
- Non-specific, sepsis-like presentation
- Progression to coma
151
Acute + chronic management of urea cycle disorders
- Acute: decrease ammonia, stop protein, give calories
| - Chronic: restrict protein
152
When do FAOD typically present?
- Once body starts to rely on fats for energy or prolonged fasting
- Neonates = >3-4 hours
- Adults = >10-12 hours
153
Classic 3 presentations for FAOD (not necessarily at diagnosis)
- Hypoglycemia
- Cardiomyopathy/arrhythmia
- Rhabdo
154
Acute + chronic management for FAOD
- Acute: stop dietary LC fat intake, given calories (dextrose)
- Chronic: LCHAD + VLCAD (fat restriction, avoidance of fasting), MCAD (avoidance of fasting)
155
Three categories of carbohydrate metabolism disorders (including main source of that particular sugar + main examples of disorders)
- Galactose (main source: lactose) = galactosemia
- Fructose (main source: sucrose) = hereditary fructose intolerance
- Glucose = glycogen storage disorders, gluconeogenic disorders
156
What IEM to think about if hypoglycemia + hepatomegaly?
GSD
157
Typical presentation of galactosemia
- Typically in the first 10 days of life with jaundice + feeding intolerance
- Progression to conjugated hyperbili, coagulopathy, liver failure
158
x4 long term complications of galactosemia
- Cataracts
- Speech apraxia
- Ataxia
- Premature ovarian failure
159
Management of galactosemia
Remove dairy products
160
Main x2 clinical findings to think about in GSD
Hypoglycemia + hepatomegaly
161
Management of hyperammonemia
- Stop protein intake
- Promote anabolism with D10W with Na/K at 1.5x maintenance, IV lipids
- Remove ammonia
- Provide deficient subtrates
162
What are the two main IEM to think about with hyperammonemia and how to differentiate them?
- Organic acid disorders = metabolic acidosis
| - Urea cycle disorders = respiratory alkalosis
163
What IEM would be revealed when testing plasma amino acids?
- Amino acid disorders
| - Urea cycle disorders
164
What IEM would be revealed when testing urine organic acids?
- Organic acid disorders
| - FAOD
165
What IEM would be revealed when testing plasma acylcarnitine?
- Organic acid disorders
| - FAOD
166
What will the results of uric acid and triglycerides be in GSD?
- Hyperuricemia
| - Hypertriglyceridemia
167
Acute + chronic management for GSD
- Acute: PO/IV glucose
| - Chronic: Avoid fasting, cornstarch
168
What IEM is at risk for liver adenomas?
GSD
169
What systems are typically involved in mitochondrial disease?
Brain, eyes, heart, muscle + endocrine
170
What is MELAS?
Mitochondrial encephalopathy, lactic acidosis, stroke-like episodes
171
Classic three features of lysosomal storage disorders?
- Coarse facial features
- Hepatosplenomegaly
- Hypertrophic cardiomyopathy
172
What eye finding is classic for lysosomal storage diseases?
Cherry red spot
173
36 month old boy with developmental delay, gout, kidney stones, self mutilation with head banging and finger biting. Inheritance pattern?
X-linked recessive = Lesch-Nyhan Syndrome
174
When to do cervical XR's for child with T21?
- No routine screening
| - Done when clinical concerns for atlantooccipital instability
175
What is (a) the normal and (b) the most severe phenotypes for alpha-1 antitrypsin?
(a) MM is the normal phenotype
- MS, SS and MZ are associated with mild to moderate deficiency
(b) ZZ and SZ are associated with severe deficiency
176
Inheritance pattern for incontinentia pigmenti?
X-linked dominant (lethal in boys)
177
x2 trinucleotide repeat disorders
- Fragile X
| - Myotonic dystrophy
178
Inheritance pattern for VACTERL
Multifactorial
179
Inheritance pattern for SMA
Autosomal recessive
180
Congenital inherited bone marrow failure syndromes - x5
```
Fanconi Anemia
Schwachman-Diamond syndrome
Dyskeratosis congenita
Pearson syndrome
Congenital Amegakaryocytic thrombocytopenia
```
181
x4 classic findings for Schwachman-Diamond Syndrome
- Steatorrhea
- FTT
- Skeletal abnormalities
- Hepatomegaly
182
What syndrome/association is choanal atresia most closely associated with?
CHARGE
183
What eye finding is most likely associated with choanal atresia?
Coloboma = key hole pupil
184
What does CHARGE stand for>
- Coloboma
- Heart
- Atresia (of nose)
- Retardation of growth/development
- GU/genital abnormalities
- Ear abnormalities
185
What syndrome is associated with abnormality with the PHOX2 gene?
Congenital hypoventilation Syndrome
186
In addition to respiratory complications, what other group of symptoms will children with congenital hypoventilation syndrome have?
Autonomic dysfunction
187
What test should we do annually for children with congenital hypoventilation syndrome?
Holter - at risk for cardiac asystole
188
x2 other associations with congenital hypoventilation syndrome?
- Neural crest cell tumors (neuroblastoma)
| - Hirschsprung's
189
Dysmorphic child with pedal edema, webbed neck, hypertrophic cardiomyopathy
Noonan's syndrome
190
Criteria for NF1
• At least 2 of:
○ 6 or more of café-au-lait macules > 5mm in prepubertal and >15mm in postpubertal
○ 2 or more neurofibromas of any type or one plexiform
○ Freckling in the axillary or inguinal regions
○ Optic glioma
○ 2 or more Lisch nodules
○ Distinctive bony lesion
First degree relative with NF1
