Metabolism Flashcards
List the 6 sphingolipidoses (lysosomal storage diseases).
- Fabry
- Tay Sachs
- Gaucher
- Niemann-Pick
- Krabbe
- Metachromatic leukodystrophy
What is the inheritance pattern of the 6 sphingolipidoses?
- Fabry - X-linked recessive
2. All others - autosomal recessive
Which sphingolipidoses are more common in the Ashkenazi Jewish population?
- Tay Sachs
- Gaucher
- Niemann-Pick
What is the most common lysosomal storage disease?
Gaucher disease
List the deficiencies causing the 6 sphingolipidoses.
- Fabry - alpha-galactosidase A
- Tay Sachs - beta-hexosaminidase A
- Gaucher - glucocerebrosidase (beta-glucosidase)
- Niemann-Pick - sphingomyelinase
- Krabbe - galactocerebrosidase
- Metachromatic leukodystrophy - arylsulfatase A
List the substances that accumulate in each of the 6 sphingolipidoses.
- Fabry - ceramide trihexoside (aka globotriaosylceramide)
- Tay Sachs - GM2 ganglioside
- Gaucher - glucocerebroside
- Niemann-Pick - sphingomyelin
- Krabbe - galactocerebroside and psychosine
- Metachromatic leukodystrophy - cerebroside sulfate
Name the deficiency and accumulation seen in Fabry disease.
Alpha-galactosidase A deficiency leads to accumulation of ceramide trihexoside (aka globotriaosylceramide)
Name the deficiency and accumulation seen in Tay-Sachs disease.
Beta-hexosaminidase A deficiency leads to accumulation of GM2 ganglioside
Name the deficiency and accumulation seen in Gaucher disease.
Glucocerebrosidase (beta-glucosidase) deficiency leads to accumulation of glucocerebroside
Name the deficiency and accumulation seen in Niemann-Pick disease.
Sphingomyelinase deficiency leads to accumulation of sphingomyelin
Name the deficiency and accumulation seen in Krabbe disease.
Galactocerebrosidase deficiency leads to accumulation of galactocerebroside and psychosine.
Name the deficiency and accumulation seen in Metachromatic leukodystrophy.
Arylsulfatase A deficiency leads to accumulation of cerebroside sulfate.
Presentation - episodic peripheral neuropathy, angiokeratomas, and hypohidrosis (early) + late progressive renal failure and cardiovascular disease
Fabry disease
Presentation - progressive neurodegeneration, developmental delay, “cherry-red” spot on macula; no hepatosplenomegaly
Tay-Sachs
Presentation - Hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of the femur, bone crises
Gaucher disease
Presentation - progressive neurodegeneration, hepatosplenomegaly, “cherry-red” spot on macula
Niemann-Pick disease
Presentation - peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy
Krabbe disease
Presentation - central and peripheral demyelination with ataxia (progressive neurodegeneration), peripheral neuropathy, dementia
Metachromatic leukodystrophy
DDx - sphingolipidoses with “cherry-red” spot on macula
Tay-Sachs (NO hepatosplenomegaly)
Niemann-Pick (hepatosplenomegaly)
Sphingolipidoses with osteoporosis, avascular necrosis of the femur, and/or bone crises
Gaucher disease (also, hepatosplenomegaly and pancytopenia)
What is the triad seen in early Fabry disease?
- Episodic peripheral neuropathy
- Angiokeratomas
- Hypohidrosis
Which sphingolipidoses has cardiovascular and renal involvement?
Fabry disease
Which sphingolipidoses presents with optic atrophy?
Krabbe disease (also, peripheral neuropathy, destruction of oligodendrocytes, developmental delay)
Key histologic finding in Tay-Sachs disease?
Lysosomes with onion skin
Compare histologic findings of Gaucher disease and Niemann-Pick disease.
Gaucher cells - lipid-laden macrophages resembling crumped paper
Niemann-Pick - lipid-laden foam cells
