USMLE COMLEX Lysosomal Storage Diseases

nonspecificstchanges's version from 2017-03-01 18:27

Lysosomal Storage Diseases

Nearly all are Autosomal Recessive EXCEPT fabry & Hunter syndrome
Niemann-Pick Disease: "You need your Sphinger to Pick your nose"


Lysosomal Storage DiseaseEnzyme DeficiencyAccumulated SubstrateInheritance PatternPathophysiology & High-Yield Associations
Tay-Sachs DiseaseHexosaminidase AGM2 gangliosideARAccumulation of cerebral ganglioside -> progressive psychomotor deteriotation, macular "cherry red spot", & ~lysosomes with "onion skinning"
Gaucher DiseaseGlucocerebrosidaseGlucocerebrosideARGaucher cells (enlarged lipid-laden histiocytes with "wrinkled tissue paper" cytoplasm) accumulate in bone, marrow, liver, & spleen, causing bone pain & fx (bone crises), osteonecrosis of femoral head, massive HSM, & pancytopenia.
Niemann-Pick DiseaseSphingomyelinasesphingomyelinARSphingomyelin accumulation in neurons & liver/spleen causes progressive psycho-motor dysfunction, macular "cherry red spots", "foamy histiocytes", & HSM.
Fabry Disease (Angiokeratoma corporis diffusum)a-Galactosidase Aceramide trihexosideXRAccumulation in vascular endothelium results in "maltese crosses" (fat bodies) in urine & renal disease, andiokeratomas, burning peripheral neuropathy, stroke, & CV disease.
Krabbe Disease (globoid cell leukodystrophy)B-Galactosidaseceramide galactoside (ie galactocerebroside)ARDemyelination & accumulation of globoid cells in CNS result in optic atrophy, peripheral neuropathy, & pyscho-motor retardation.
Metachromatic leukodystrophyArylsulfatase ACerebroside sulfatidesARSulfatide accumulation & central & peripheral demyelination result in ataxia & psychomotor degeneration & dementia in adults.
Hurler Syndrome (mucopolysaccharidosis type I H)a-L-Iduronidasen/aARAccumulation of GAGs lead to coarse facial features (gargoylism), Hepatosplenomegaly, mental retardation, joint & skeletal abnormalities, cardiac disease, & Corneal Clouding.
Hunter Syndrome (mucopolysaccharidosis type II)Iduronate sulfatasen/aXRSame features of Hurler but with milder mental retardation with aggressive behavior & NO corneal clouding.