Inborn error of Metabolism Flashcards
Cutaneous and subcutaneous neurofibromas
Cafe au lait spots
Lisch nodules (pigmented nodules of the iris)
Freckles in groin or axilla
Gliomas of optic nerve
Skeletal lesions: thinning of the cortices of long bones
Loss of GAP (GTPase activating proteins) activity permits uncontrolled activation
Autosomal dominant, mutation of what gene/chromosome??
Neurofibromatosis Type I (gene is NF1 on 17)
Bilateral tumors of CN VIII (acoustic neuromas)
Juvenile cataracts
Meningiomas
Gliomas
Ependymomas
LOH of gene coding tumor suppressor merlin/schwannomin
Mutation of what gene/chromosome #?
Neurofibromatosis Type 2
Gene NF2 on Chrom 22 (Think Type 2 = 22)
Deficient Homogentisate oxidase (pathway of tyrosine to fumarate)
Homogentisate substrate accumulates (toxic to cartilage)
BLACK URINE and cartilage when exposed to air/light (check First Aid/goljian)
Degenerative arthritis
Autosomal recessive, benign disease
Inborn error of metabolism?
Alkaptonuria
Deficient GALT (galactose-1-P uridyltransferase)
Galactose-1-P accumulates (toxic to liver, CNS)
Galactose (in urine), Galactitol (alcohol sugar causes osmotic damage)
Mental retardation, cirrhosis, hypoglycemia, cataracts, AVOID DAIRY PRODUCTS I
nborn error of metabolism?
Galactosemia
Deficient Aldolase B
Fructose 1-P accumulates (toxic) accumulates
Cirrhosis, hypoglycemia, hypophosphatemia, AVOID FRUCTOSE/SUCROSE
Inborn error of metabolism?
Hereditary fructose intolerance
Deficient cystathionine synthase
Homocysteine and methionine accumulates
Mental retardation, vessel thrombosis, lens dislocation, arachnodactyly, tall stature, kyphosis, atherosclerosis (stroke and MI)
Decrease methionine, increase cysteine, increase B12 and folate in diet.
Inborn error of metabolism?
Homocystinuria
Also 2 other types
1) Cystationine synthase deficiency
2) Decrease affinity of cystathionine synthase for pyridoxal phosphate (B6)
3) Homocyteine methyltransferase deficiency
Deficient branched chain alpha-ketoacid dehydrogenase
Leucine, valine, isoleucine and their ketoacids accumulate
Mental retardation, seizures, feeding problems, SWEET SMELLING URINE
Maple Syrup Urine Disease
Remember this: I Love Vermont maple syrup from maple trees with branches.
Deficient phenylalanine hydroxylase
Phenylalanine accumulates (toxic)
Restrict Phe in food, add tyrosine to diet
Inborn error of metabolism?
PKU (Phenylketonuria)
If pregnant woman has PKU: Phe free diet is compulsory otherwise fetus will be mentally retarded
Deficient Muscle glycogen phosphorylase (autosomal recessive)
Accumulation of glycogen
Glycogenosis, muscle fatigue, no lactic acid increase with exercise
MUSCLE CRAMPS and SPASMS during EXERCISE, myoglobinuria
Inborn error of metabolism?
McArdle’s Disease
McArdle = Muscle
Deficient alpha-1,4,-glucosidase (lysosomal enzyme) (autosomal recessive)
Accumulation of glycogen
Cardiomegaly with early death (<2 yo)
Inborn error of metabolism?
Pompe Disease
Pompe trashed the Pump *heart, liver, muscle
Deficient Glucose-6-phosphatase (gluconeogenic enzyme) (Autosomal recessive)
Glucose-6-phosphate accumulation
Glycogenosis, enlarged liver and kidneys, hypoglycemia (no response to glucagon)
NORMAL Mental development & Longevity
Inborn error of metabolism?
Von Gierke Disease
Deficient glucocerebrosidase (Autosomal recessive)
Accumulation of glucocerebroside
Hepatosplenomegaly, Fibrillar-appearing macrophages in liver, spleen, and bone marrow, aseptic necrosis of femur, bone crises, pancytopenia
Inborn error of metabolism?
Adult type (Gaucher’s disease)
Deficient a-L-Iduronidase
Accumulation of dermatan and heparan sulfate
Mental retardation, coarse facial and short neck
Inborn error of metabolism?
Hurler’s Syndrome
Deficient Sphingomyelinase (Autosomal Recessive)
Accumulation of Sphingomyelin
Mental retardation, hepatosplenomegaly, foamy macrophages (lipid laden), hepatosplenomegaly, cherry red spot on macula
Inborn error of metabolism?
Niemann-Pick Disease
Deficient Hexosaminidase A (Autosomal Recessive)
Accumulation of GM2, ganglioside
Muscle weakness, cherry-red macula, blindness, lysosomes with onion skin, NO Hepatosplenomegaly
Inborn error of metabolism?
Tay-Sachs disease
You got this! Flip the card for a special surprise. Click the link! (It’s not porn, sorry)
Fibrillin-1 gene mutation (autosomal dominant)
CT disorder
Tall with long extremeties, pectus excavatum, hypermobile joints, long tapering fingers and toes (arachnodactyly)
Cystic medial necrosis of aorta (floppy mitral valve, aortic incompetence, and dissectinc AA)
Subluxation of lenses (Upward and temporally)
Syndrome?
Marfan Syndrome
Neurocutaneous disorder
Numerous benign HAMARTOMAS: Harmartomas in CNS, Angiofibromas, Mitral regurgitation, Ash-leaf spots, cardiac Rhabdomyoma; Tuberous sclerosis, autosomal dOminant, Mental retardation, renal Angiomyolipoma, Seizures, Shagreen patches.
Increased incidence of subependymal astrocytomas and ungual fibromas
Incomplete penetrance, variable expression
Autosomal Dominant
Tuberous Sclerosis
Cavernous hemangiomas in skin, mucosa, organs
bilateral renal cell carcinomas
hemangioblastoma (high vascularity with hyperchromatic nuclei) in retina, brain stem, cerebellum
pheochromocytoma
Autosomal dominant
Deletion of gene on which chromosome? Constitutive expression of what?
von Hippel-Lindau disease
VHL on Chromosome 3, expression of HIF resulting in activation of angiogenic growth factors
What is this crazy First Aid mneumonic helping you remember?
Be Wise, Fool’s GOLD Heeds Silly HOpe
X-linked Recessive Disorders!
Bruton agammaglobulinemia
Wiskott-Aldrich syndrome
Fabry Disease
G6PD deficiency
Duchenne (and becker) muscular dystrophy
Hunter Syndrome
Hemophilia A &B
Ornithine transcarbamylase deficiency
Mneumonic: Very Poor Carbohydrate Metabolism
VonGierke Disease
Pompe Disease
Cori disease (milder vonGierke, normal blood lactate in this)
McArdle Disease
Deficient alpha-galactosidase A (X-linked Recessive)
Accumulation of ceramide trihexoside
Peripheral neuropathy of hands/feet
Angiokeratomas
Cardiovascular/renal disease
Fabry Disease
