Sphingolipidoses Flashcards
What is the inheritance pattern of all the sphingolipidoses with the exception of Fabrys?
AR or X linked recessive
What is the inheritance pattern of Fabrys?
XLR
Deficiency in Fabry disease?
α-galactosidase A
Accumulated substrate in Fabry disease?
- ceramide trihexoside (globotriaosylceramide)
Symptoms of Fabry disease?
- angiokeratomas
- peripheral neuropathy
- glomerulopathy
What is the deficiency in Tay-Sachs disease?
β-hexominidase A
Definition of sphingolipidoses?
metabolic storage disorders characterized by accumulation of harmful quantities of glycosphingolipids and phosphosphingolipids …. (lipids)
What is the accumulated substrate in Tay-Sachs disease?
GM2 (ganglioside)
Symptoms of Tay Sachs?
- macular cherry-red spot
- progressive neurodegeneration
What is the deficiency in Gaucher disease?
β - glucocerebrosidase
What is the accumulated substrate in Gaucher disease?
glucocerebroside
What are key features of Gaucher disease?
- hepatosplenomegaly
- pancytopenia
- bone pain/osteopenia
What is the deficiency found in Niemann-Pick disease?
Shingomyelinase
What is the accumulated substrate in Niemann-Pick disease?
Sphingomyelin
What are key features of Niemann-Pick disease?
- macular cherry- red spot
- progressive neurodegeneration
- hepatosplenomegaly
What is the deficiency found in Krabbe disease?
galactocerebrosidease deficiency
What is the accumulated substrate in Krabbe disease?
galactocerebroside psychosine
What are key features of Krabbe disease?
- progressive neurodegeneration
- peripheral neuropathy
- optic atrophy
What is the deficient enzyme in metachromatic leukodystorphy?
arylsufatase A
What is the accumulated substrate in metachromatic leukodystrophy?
cerebroside sulfate
What are the symptoms of metachromatic leukodystrophy?
- progresive neurodegeneration
- peripheral neuropathy
Hurler Syndrome deficient enzyme?
alpha L iduronidase
Accumulated substrate of alpha L iduronidase?
dermatan & heparin sulfate
Symptoms of Hurler syndrome? (death usually caused by cardiac complications)
- severe developmental delay & intellectual disability
- coarse facial features
- corneal clouding
- hepatosplenomegaly
- death at age < 10 (cardiac complications)
What is the inheritance pattern of Hunter syndrome?
XLR
What is the deficient enzyme in Hunter syndrome?
idruonate sulfatase
What are some key features of Hunter syndrome?
- milder features than Hurler:
- (+) aggressive behavior
- (-) corneal clouding
- death in adolescence/ early adulthood
What is mucopolysaccharidoses?
lysosomal storage disorders resulting from defective metabolism of glycosaminoglycans (GAGs)
What are GAGs?
long unbranched polysaccharides that are an important component of ground substance within the extracellular matrix of connective tissues
