Symptoms
hypohidrosis, angiokeratomas, renal failure, peripheral neuropathy
Fabry disease
enzyme deficiency? what is accumulated?
central and peripheral demyelination, ataxia, dementia
metachromatic leukodystrophy
enzyme def: arylsulfatase A
accum: cerebroside sulfate
rate limiting step?
glycine + succinyl-coa --> ALA
ALA synthase
first step
which vitamin and medication deficiency (and anemia/inheritance) inhibits ALA synthase?
blood smear findings?
burton lines (blue-black line in gums), metaphyseal lines on x-ray, basophilic stippling
lead poisoning
main amino acid in collagen synthesis
GLYCINE (also proline and lysine)
Osteoporosis, AVN femoral head, lipid-laden tissue paper cytoplasm
Gaucher
enzyme deficiency: glucocerebrosidase
accumulation: glucocerebroside
alpha-galactosidase A
fabry
accumulated: ceramide trihexoside
ALA dehydratase deficiency disease?
inhibits: ALA to porphobilinogen
lead also inhibits ferrochelatase (protoporphyrin to heme) the last step
pain, polyneuropathy, port wine colored urine, p450 inducers (phenytoin, barbs, sulfonamides), psychological sxs
acute intermittent porphyria
lack of hydroxylation of proline/lysine results in what disease?
scurvy
vitamin c required for hydroxylation
cherry-red macula, onion skin lysosomes, NO hepatosplenomegaly
Tay-sachs
enzyme deficiency: hexosaminidase A
accumulation: GM2-ganglioside
if we have hepatosplenomegaly which disorder would it be?
galactocerebrosidase
krabbe
accumulated?
porphobilinogen deaminase catalyzes
porphobinilogen to hydroxymethylbilane
disease?
blistering hyperpigmentation, photosensitivity, worsened by EtOH, hep c
porphyria cutanea tarda
tx: phlebotomy, low dose hydroxycloroquine
defect in GLYCOSYLATION of lysine hydroxyl groups?
osteogenesis imperfecta (which collagen type?)
globoid cells, oligodendrocyte destruction, optic atrophy
Krabbe disease
enzyme def: galactocerebrosidase
accumulated: galactocerebroside
arylsulfatase A
metachromatic leukodystrophy
accumulated: cerebroside sulfate
porphyria cutanea tarda deficiency?
iron overload, hepatitis c, heavy alc consumption inhibits this enzyme
labs: increased iron, ferritin
decreased TIBC
sideroblastic anemia
Tx?
defect in disulfide cleavage and lack of tropocollagen?
cherry-red macula, foam cells (lipid-laden macrophages), YES hepatosplenomegaly
Niemann-pick disease
enzyme def: sphingomyelinase
accum: sphingomyelin
hexosaminidase A
tay-sachs
accumulated?
defect in lysyl oxidase and cross-linking of tropocollagen?
requires copper
Menkes disease