BCEM Flashcards
Orotic Aciduria
Inher, Mech, Pres (Epi + 4), Micro Finding, RX?
AR.
Defect in UMP Synthase ->
Inability to convert Orotic acid -> UMP
(De Novo Pyrimidine Syn pathway).
PRES: Children
- Failure to thrive
- Megaloblastic Anemia CAN’T be cured by Vit B9 or B12
- Glossitis
- Orotic acid in urine
FINDING:
- Hypersegmented Neutrophils
RX = UMP (allows bypassing of mutated enzyme)
a-amanitin Ingestion
(found in Amanita phalloides = “death cap” mushrooms)
Mech & Pres?
Inhibits RNA Polymerase II -> Severe hepatotoxicity
I-Cell (Inclusion Cell) Disease
Classification, Mech (3 steps), Pres (3), Labs?
Inherited. Lysosomal Storage Disorder.
MECH:
Defect in Phosphotransferase -> Failure of Golgi to phosphorylate MANNOSE residues on glycoproteins (ie↓mannose-6P) -> Proteins secreted extracellularly rather than delivered to lysosomes.
** Often fatal in childhood. **
PRES:
- Coarse facial features
- Clouded corneas
- Restricted joint movement
LABS:
- High lysosomal enzymes
Chediak-Higashi Sx
Genetics, Mech (2), Pres (3)?
Mutation in LYST gene (lysosomal trafficking regulator).
- ↓fusion of lysosomes & phagosomes
- ↓microtubule sorting of endosomal proteins
Kartagener’s Sx (1ry ciliary dyskinesia)
Mech, Pres (4), Comp?
Immotile cilia due to defective dynein arm.
PRES:
- Infertility (ie immotile sperm and dysfunctional fallopian tube cilia)
- Situs Inversus
- Bronchiectasis
- Chronic Sinusitis (particles and bacteria not pushed out)
COMP:
-↑risk of ectopic pregnancy
Osteogenesis Imperfecta (“Brittle Bone Disease”)
Def’n, Inher, Mech, Pres (4)?
Congenital defect of bone RESORPTION -> structurally WEAK bone.
AD.
Deficiency (↓production) of Type 1 Collagen.
Inability to form Procollagen (defective glycosylation of
pro-a-chain hydroxylysine).
PRES:
- “Blue sclera” (thin collagen on sclera => can see underlying
choroidal veins = blue.
THINK: You can see veins under thin skin.)
- Multiple bone fractures with minimal trauma (may occur during birth)
- Hearing loss (fracturing of middle ear bones = ossicles)
- Dental imperfections (lack of dentin)
** May be confused with child abuse **
Ehlers-Danlos Sx
Def’n, Mech (2 steps), Inher, Classification (3 types),
Pres (3), Comp / Assoc (3)?
Deficiency of Type III Collagen (faulty synthesis).
Mutation in Type V Collagen ->
Defective Tropocollagen CROSS-LINKING.
Autosomal.
CLASSIFICATION:
- Hypermobility type
- Classical type (mutation in Type V Collagen -> joint + skin pres)
- Vascular type (Type III Collagen def -> vascular + organ pres)
PRES:
- Hypermobile joints
- Elastic skin
- Easy bruising / tendency to bleed
COMP / ASSOC:
- Aortic + Berry Aneurysms
- Organ rupture
- Joint dislocation
Menkes Dz
Def’n, Mech (2 steps), Pres (3)?
Connective tis dz.
Impaired Cu abs + transport ->↓activity of Lysyl Oxidase.
PRES:
- “Brittle + kinky hair”
- Growth retardation
- Hypotonia
Alport Sx
Mech (2), Inher, Pres (3)?
- Defective Type IV Collagen due to mutation.
- Thin + split GLOMERULAR BM -> defective ability to filter blood.
XR (MC)
PRES:
- Deafness
- Cataracts / ocular disturbances
- Nephritic Sx
Marfan Sx
Mech, Pres (5), Comp (2)?
Fibrillin defect (Fibrillin-1 mutation).
PRES:
- “Tall with long extremities” + Arachnodactyly (abnormally long + slender fingers and toes)
- Hyperflexible / hypermobile joints
- Lens dislocation + subluxation (usually upward + temporally)
- Aortic incompetence (due to cystic medial necrosis of aorta)
- Floppy Mitral valve
COMP:
- Dissecting Aortic Aneurysm / Berry Aneurysm
- Mitral
Familial Hypercholesterolemia
Mech (2 steps), Pres (2)?
Absent / defective LDL receptor ->↑LDL.
PRES:
- Severe atherosclerosis early in life
- Achilles tendon xanthoma
Mitochondrial Myopathies
List (3), Micro Finding?
- Leber’s Hereditary Optic Neuropathy (acute loss of central vision)
- Myoclonic Epilepsy
- Mitochondrial Encephalopathy
FINDING:
- “Ragged red fibers”
Cystic Fibrosis
* MC lethal genetic dz in Caucasians*
Inher, Genetics, Mech (5 steps, 3 effects),
DX, Comp (8: 2 Resp, 4 GI, 1 Repro, 1 Vit), RX (2)?
AR.
Defect in CFTR, chr 7.
MECH:
Defective CFTR ->
Defective Cl channels in lungs, GI tract + sweat glands ->
↑intracel Cl ->
Compensatory↑Na + H20 reabs ->
ECF Na + H20 losses / RENAL K + H wasting.
(Analogous to taking Loop Diuretic)
- THICK MUCUS secreted into lungs + GI tract
- Hypokalemia
- Contraction Alkalosis
DX:
-↑Cl (> 60) in sweat
COMP:
- Recurrent pulm infections and chronic bronchitis / bronchiectasis
- Nasal polyps
- Meconium Ileus in newborns
- Malabsorption / Steatorrhea
- Cholesterol Stones
- Pancreatic insuf
- Infertility in Males (absent sperm)
- Vit A, D, E, K deficiencies
RX:
- N-acetylcysteine (to cleave disulfide bonds w/in mucus glycoproteins)
- DNAse / Dornase Alfa (to clear leukocytic debris)
McCune-Albright Sx
Mech, Pres (4)?
Mosaic G-protein signaling mutation.
PRES:
- Endocrine abnormalities
- Precocious Puberty
- Cafe-au-Lait spots
- Polyostotic fibrous dysplasia
Muscular Dystrophies
3 Types, Inher, General Pres (2)?
- Duchenne
- Becker
- Myotonic Type I
INHER: XR (Duchenne + Becker’s)
GENERAL PRES:
- Muscle wasting
- Myotonia
Duchenne Muscular Dystrophy
Genetics, Pres (Epi + 2), Lab Findings (2), DX (2), Comp?
FRAMESHIFT Deletion of Dystrophin gene.
PRES: Onset before 5 yrs
- Weakness in pelvic girdle muscles that progresses superiorly
- Pseudohypertrophy of calf muscles (due to fibrofatty replacement of muscle) -> Gower Maneuver
LABS:
- ↑Aldolase
- ↑CPK
DX:
- Western Blot
- Muscle biopsy
COMP:
- Dilated Cardiomyopathy
Becker Muscular Dystrophy
Genetics, Pres (Epi)?
POINT mutation in Dystrophin gene.
PRES: Onset in adolescence / early adulthood
* Less severe than Duchenne *
Myotonic Type I Dystrophy
Genetics, Pres (4)?
CTG trinucleotide repeat expansion in DMPK gene ->
Abnormal expression of Myotonin protein kinase.
PRES:
- Frontal balding
- Cataracts
- Arrhythmia
- Testicular atrophy
Fragile X Sx
Genetics, Pres (4)?
Trinucleotide repeat disorder (CGG) ->
Defect affecting expression and methylation of FMR1 gene.
PRES:
- Long face with large jaw + large everted ears
- Autism
- Mitral Prolapse
- Testes enlarged
Down Sx (Trisomy 21)
Genetics,
Pres (7: THINK: 4 above heart, heart, 2 below heart ),
1st Trimester U/S Findings (2), 2nd Trimester Quad Screen (4),
Comp (3)?
- Meiotic ND (95%. Assoc w advanced maternal age)
- Robertsonian Translocation (4%)
- Mosaicism (1%)
PRES:
- Intellectual disability
- Flat facies and “single palmar crease”
- “Gap between first two toes”
- Brushfield Spots in eyes
- Congenital HD (ASD or VSD)
- Duodenal Atresia
- Hirschsprung Dz
1st TRIMESTER U/S:
- ↑nuchal translucency + hypoplastic nasal bone
- PAPP-A↓
QUAD SCREEN:
- a-fetoprotein↓
- b-HCG↑
- Estriol↓
- Inhibin A ↑
COMP:
- ASD (due to defects in ostium primum) + VSD
- ALL + AML (AML usually before age 5)
- Alzheimer’s
Edwards Sx (Trisomy 18)
Pres (Epi + 6: 3 above heart, heart, 2 re extremities),
1st Trimester U/S Finding, 2nd Trimester Quad Screen (4)?
PRES: Infant. Death usually within 1 yr of birth.
- Microcephaly
- Severe intellectual disability
- Micrognathia (small jaw), low-set ears + prominent occiput
- Congenital HD
- Clenched hands
- “Rocker-bottom” feet
1st TRIMESTER U/S:
- PAPP-A ↓
QUAD SCREEN: Everything ↓
- a-fetoprotein↓
- b-HCG↓
- Estriol↓
- Inhibin A↓or normal
Patau Sx (Trisomy 13)
Pres (Epi + 6: 3 above heart, heart, 2 re extremities),
1st Trimester U/S Findings (2)?
PRES: Infant. Death usually within 1 yr of birth.
- Microcephaly / Holoprosencephaly
- Severe intellectual disability
- Microphthalmia + Cleft Lip / Palate
- Congenital HD
- Polydactyly
- “Rocker-bottom” feet
1st TRIMESTER U/S:
- ↑nuchal translucency
- PAPP-A↓
Williams Sx
Genetics, Pres (2), Lab Findings, Comp?
Congenital microdeletion of chr 7 long arm (incl Elastin gene).
PRES:
- Intellectual disability, however good verbal skills and extreme friendliness with strangers
- “Elfin” facies
LABS:
- Hypercalcemia (↑sensitivity to Vitamin D)
Turner Sx (45 XO)
Pres (7)?
PRES:
- Cystic Hygroma (cystic lymphatic lesion) at birth
- Congenital Heart Disease
- Lymphedema
- Short stature
- “Webbed neck”
- “Horseshoe kidney”
- “Streak ovaries”
Angelman’s Sx
Mech, Genetics, Pres (4)?
Maternal allele should be active, however is not expressed.
Paternal allele inactivated.
Imprinting / Uniparental Disomy.
PRES: “Happy puppet”
- MR
- Inappropriate laughter
- Seizures
- Ataxia
Prader-Willi Sx
Mech, Genetics, Pres (5)?
Paternal should be active, however is not expressed.
Maternal allele inactivated.
Imprinting / Uniparental Disomy.
PRES:
- MR
- Obesity
- Hyperphagia
- Hypotonia
- Hypogonadism
Glycogen Storage Diseases
4 Subtypes, Etiology, Path, Inher?
- Von Gierke (Type I)
- Pompe (Type II)
- Cori (Type III)
- McArdle (Type V)
ET = Enzyme deficiencies
PATH = Abnormal Glycogen METAB -> ACCUM of Glycogen in cells.
AR.
Von Gierke Disease (Type I)
Deficient Enz, Mech, Pres (2), Labs, RX?
Def Enz = Glucose-6-Phosphatase.
MECH:↑Glycogen in Liver.
PRES:
- Severe fasting hypoglycemia
- Hepatomegaly
RX: Frequent oral glucose / cornstarch.
Avoidance of fructose + galactose
Pompe Disease (Type II)
Deficient Enz, Locations Affected (3), Pres (2), Prog?
Def Enz = Lysosomal a-1,4-glucosidase (acid maltase) def.
- Muscle
- Heart
- Liver
PRES:
- Infantile Hypertrophic Cardiomyopathy
- Exercise Intolerance
PROG = early death.
Cori Disease (Type III)
Deficient Enz, Def’n?
Def Enz = a-1,6-glucosidase (Debranching Enz).
MILDER form of Type I / Von Gierke’s. Gluconeogenesis intact.
** Normal Lactate levels **
McArdle Disease (Type V)
Def Enz, Mech, Pres (2), Urine?
Def Enz = Myophosphorylase (skeletal muscle glycogen phosphorylase).
MECH:↑Glycogen in Muscle, however can’t break it down.
PRES:
- Painful muscle cramps / fatigue / myalgias
- Arrhythmias (due to electrolyte abnormalities)
URINE: Myoglobinuria
Lysosomal Storage Diseases
2 Subtypes, Etiology, Path, Inher, Common Pres (4)?
- Sphingolipidoses
- Mucopolysaccharidoses (Hurler + Hunter Sx)
ET = Lysosomal enz def.
PATH = Accum of abnormal substrates.
AR EXCEPT Fabry + Hunter (XR).
PRES:
- Devel delay (T-S + Krabbe + Hurler/Hunter)
- Progressive neurodegeneration (N-P + T-S)
- Peripheral neuropathy (Fabry + Krabbe)
- Hepatosplenomegaly (Gaucher + N-P + Hurler/Hunter)
Fabry Dz
Def Enz / Substrate Accum, Pres (3)?
Def Enz = a-galactosidase A. Substrate = Ceramide trihexoside.
PRES: THINK: CARDIO
- CV / Renal dz
- Angiokeratomas
- Peripheral neuropathy
Gaucher Disease
Def Enz / Substrate Accum, Locations (4), Pres (3), Micro Finding?
Def Enz = b-glucosidase / Glucocerebrosidase.
Substrate = Glucocerebroside.
- Brain
- BM
- Spleen
- Liver
PRES:
- Pancytopenia
- Hepatosplenomegaly
- Bone crises (eg “aseptic necrosis of femur”)
FINDING: Gaucher cells
Niemann-Pick (N-P) Dz vs Tay-Sachs (T-S) Dz
Def Enz / Substrate Accum (N-P vs T-S), Common Pres (3), Distinguishing Pres (N-P), Micro Finding (N-P vs T-S)?
N-P: Sphingomyelinase / Sphingomyelin.
T-S: Hexosaminidase A / GM2 Ganglioside.
COMMON PRES:
- Devel delay
- Progressive neurodegeneration
- “Cherry-red spot on macula”
- Hepatosplenomegaly (N-P ONLY)
FINDINGS:
- N-P: Foam cells
- T-S: Lysosomes with “onion skin”
Krabbe Dz
Def Enz / Substrate Accum, Pres (3), Micro Finding?
Def Enz = Galactocerebrosidase.
Substrate = Galactocerebroside psychosine.
PRES:
- Optic atrophy
- Devel delay
- Peripheral neuropathy
FINDING: Globoid cells
Metachromatic Leukodystrophy
Def Enz / Substrate Accum, Pres (3)?
Def Enz = Arylsulfatase A. Substrate = Cerebroside sulfate.
PRES: THINK: NEURO
- Demyelination
- Dementia
- Ataxia
Hurler vs Hunter Sx
Def Enz (vs) / Substrate Accum (2), Inher (vs), Common Pres (4), Distinguishing Pres (vs)?
Hurler: a-L-iduronidase
Hunter: Iduronate sulfatase
Substrates = Dermatan sulfate + Heparan sulfate.
AR (Hurler) vs XR (Hunter).
COMMON PRES:
- Devel delay
- “Gargoylism”
- Hepatosplenomegaly
- Airway obstruction
- Corneal clouding (Hurler)
- Aggression (Hunter)
Classic Galactosemia
Def’n, Path, Pres (4), Comp (2), RX?
Absence of galactose-1-P uridyltransferase.
PATH = Accum of toxic substances (ie galactitol).
PRES:
- Failure to thrive
- Intellectual disability
- Infantile Cataracts
- Hepatomegaly + Jaundice
COMP:
- Phosphate depletion
- E coli sepsis (Neonates)
RX = Exclusion of galactose + lactose from diet
Urea Cycle Enzyme Deficiencies (2)
Pres?
- N-acetylglutamate def / Carbamoyl P Synthetase I def
- Ornithine Transcarbamylase def
PRES:
- Hyperammonemia
Hyperammonemia
Etiologies (2), Mech (3 steps), Pres (6), RX (3)?
ET:
- Hereditary (eg Urea Cycle enzyme def)
- Acquired (eg Liver dz)
Excess NH4 -> Depletion of a-ketoglutarate -> Inhib of TCA Cycle.
PRES: (‘Ammonia Intoxication’)
- Cerebral Edema
- Somnolence
- Asterixis (tremor)
- Blurred vision
- Slurred speech
- Vomiting
RX:
- Limit protein in diet
- Benzoate / Phenylbutyrate (bind a.a -> excretion -> ↓NH4)
- Lactulose (acidification of GI tract -> NH4 trapping -> excretion)
Ornithine Transcarbamylase Deficiency
Inher, Mech, Pres (Onset + 1), Labs (2)?
XR (*unlike other ‘urea cycle enz def’ which are AR).
EXCESS Carbamoyl P -> Orotic acid.
PRES: First few days of life, however sometimes later.
- Hyperammonemia
LABS:
- Orotic acid↑in bl / urine
- BUN ↓
Phenylketonuria (PKU)
Subtypes (2), Inher, Mech (3 steps),
Pres (6), Urine, Screening / DX, RX (2 dietary)?
- Maternal (-> pres in infant)
- Malignant (↓tetrahydrobiopterin cofactor, NOT ph hydroxylase)
AR.
↓phenylalanine hydroxylase (= tyrosine becomes essential) ->
↑phenylalanine -> Excess phenylketones in urine.
PRES:
- Growth retardation
- Intellectual disability
- Seizures
- “Musty body odor” (disorder of AROMATIC a.a metab)
- Fair skin
- Eczema
URINE: Excess Phenylketones
SCR = 2-3 days after birth
RX:
- ↑Tyrosine in diet (Tyrosine becomes essential)
- ↓Phenylalanine in diet (eg aspartame)
Maternal PKU
Etiology, Pres (in INFANT: 4)?
ET = Lack of proper dietary therapy during pregnancy.
PRES (INFANT):
- Growth retardation
- Microcephaly
- Intellectual disability
- Congenital HD
Alkaptonuria / Ochronosis
Def’n, Inher, Pres (4)?
Congenital def of Homogentisate Oxidase.
(Enz in degradative pathway of tyrosine -> fumarate)
AR.
PRES: Benign. THINK: DARK
- Dark connective tis
- Brown sclerae
- Urine turns black on exposure to air
- Arthralgias (homogentisic acid toxic to cartilage)
Albinism
Def’n, Etiology, Comp?
↓Tyrosine + Melanin.
Congenital def of either:
- Tyrosinase (no tyrosine -> melanin)
- Tyrosine transporters
ET (possible) = lack of migration of neural crest cells.
COMP =↑risk of skin cancer.
Homocystinuria
Subtypes (3), Inher, Path,
Urine, Pres (7: 2 Neuro, 2 CV, 3 MSK)?
- Homocysteine Methyltransferase / Methionine Synthase def
- Cystathionine Synthase def
- ↓AFFINITY of Cystathionine Synthase for Pyridoxal P
AR.
PATH = Excess Homocysteine.
URINE = Excess Homocysteine.
PRES:
- Intellectual disability
- Lens subluxation
- Atherosclerosis (-> MI, Stroke)
- Thrombosis
- Tall stature
- Kyphosis
- Osteoporosis
Cystinuria
Path, Locations (2), Inher,
Urine, DX, RX (3: 2 Meds)?
PATH = Defect of A.A transporters for “COLA”: Cysteine, Ornithine, Lysine, Arginine.
- Transporter in Renal PCT
- Transporter in Intestine
AR. Common
URINE: Hexagonal Cystine stones (due to excess cystine in urine)
DX: Urinary Cyanide-Nitroprusside test
RX:
- Urinary Alkalinization (Acetazolamide, Potassium Citrate)
- Chelating agents (↑solubility of cystine stones)
- Good hydration
Maple Syrup Urine Disease
Etiology, Path (3 steps), Urine, Pres?
ET = Vit B1 / a-ketoacid dehydrogenase def
PATH:
↓a-ketoacid dehydrogenase ->
Blocked degradation of BRANCHED A.A (Isoleucine, Leucine, Valine) ->
↑a-ketoacids in bl (esp Leucine).
URINE: “Smells like maple syrup / burnt sugar”
PRES: Intellectual disability + severe CNS defects. Death.
Hyperchylomicronemia (Type I Familial Dyslipidemia)
Mech (2), Inher, Pres (3), Labs (3)?
- Lipoprotein lipase def
- Apolipoprotein C-II alteration
AR (other familial dyslipidemias = AD).
PRES:
- Hepatosplenomegaly
- Pancreatitis
- Eruptive / pruritic xanthomas
LABS: ↑in:
- Chylomicrons
- Cholesterol
- Trigylcerides
Familial Hypercholesterolemia (Type IIA Familial Dyslipidemia)
Mech, Genetics (Hetero vs Homo), Pres (3), Labs (2)?
Absent / defective LDL receptors.
GEN:
- Hetero: Chol ~ 300 mg/dL
- Homo: Chol > 700 mg/dL (very rare)
PRES:
- Accelerated Atherosclerosis (eg “MI before age 20”)
- Corneal Arcus
- Achilles xanthomas
LABS: ↑in:
- Cholesterol
- LDL
Hypertriglyceridemia (Type IV Familial Dyslipidemia)
Mech, Pres, Labs (2)?
HEPATIC overproduction of VLDL.
PRES:
- Pancreatitis
LABS: ↑in:
- VLDL
- Triglycerides
Lesch-Nyhan Sx
Mech, Pres (Epi + 3)?
HGPRT def.
PRES: Boy
- Gout
- Intellectual disability
- Self-mutilating behavior
Kwashiorkor (Malnutrition)
Def’n, Pres (4)?
PROTEIN malnutrition.
PRES: “Small child w swollen belly”
- Liver malfunction (↓apolipoprotein syn -> fatty change)
- Anemia
- Edema
- Skin lesions
Marasmus (Malnutrition)
Def’n, Pres?
ENERGY malnutrition.
PRES:
- Tis/muscle wasting + loss of subcutaneous fat
- Variable edema
