Sphingolipidoses

Question 1

Fabry disease

Answer 1

• XR
• alpha-galactosidase A —- increased Ceramide trihexose
• Peripheral neuropathy (hands/feet), angiokeratomas, CV/renal disease

Question 2

Gaucher disease (most common)

Answer 2

• Glucocerebrosidase (beta-glucosidase) — increased glucocerebroside
• hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crisis, Gaucher cells (lipid-laden macros resembling crumpled tissue paper)
• Rx: recombinant glucocerebrosidase

Question 3

Niemann-Pick disease

Answer 3

• Sphingomyelinase —- increased sphingomyelin
• Progressive neurodegeneration, hepatosplenomegaly, foam cells (lipid-laden macros), cherry red spot on macula, loss of previously acquired motor abilities, hypotonia/blind by 1yo
• death by 3yo

Question 4

Tay-Sachs disease

Answer 4

• Hexosaminidase A —-GM2 ganglioside
• Progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, NO hepatosplenomegaly (vs. Neimann Picks)

Question 5

Krabbe disease

Answer 5

• Galactocerebrosidase —- increased galactocerebroside, psychosine
• Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Question 6

Metachromatic leukodystrophy

Answer 6

• Arylsulfatase A —-increased cerebroside sulfate (sulfatides) [stain brown when stained with toluidine blue]
• Central and peripheral demyelination with ataxia, dementia