Metabolism

Question 1

List the 6 sphingolipidoses (lysosomal storage diseases).

Answer 1

1. Fabry
2. Tay Sachs
3. Gaucher
4. Niemann-Pick
5. Krabbe
6. Metachromatic leukodystrophy

Question 2

What is the inheritance pattern of the 6 sphingolipidoses?

Answer 2

1. Fabry - X-linked recessive

2. All others - autosomal recessive

Question 3

Which sphingolipidoses are more common in the Ashkenazi Jewish population?

Answer 3

1. Tay Sachs
2. Gaucher
3. Niemann-Pick

Question 4

What is the most common lysosomal storage disease?

Answer 4

Gaucher disease

Question 5

List the deficiencies causing the 6 sphingolipidoses.

Answer 5

1. Fabry - alpha-galactosidase A
2. Tay Sachs - beta-hexosaminidase A
3. Gaucher - glucocerebrosidase (beta-glucosidase)
4. Niemann-Pick - sphingomyelinase
5. Krabbe - galactocerebrosidase
6. Metachromatic leukodystrophy - arylsulfatase A

Question 6

List the substances that accumulate in each of the 6 sphingolipidoses.

Answer 6

1. Fabry - ceramide trihexoside (aka globotriaosylceramide)
2. Tay Sachs - GM2 ganglioside
3. Gaucher - glucocerebroside
4. Niemann-Pick - sphingomyelin
5. Krabbe - galactocerebroside and psychosine
6. Metachromatic leukodystrophy - cerebroside sulfate

Question 7

Name the deficiency and accumulation seen in Fabry disease.

Answer 7

Alpha-galactosidase A deficiency leads to accumulation of ceramide trihexoside (aka globotriaosylceramide)

Question 8

Name the deficiency and accumulation seen in Tay-Sachs disease.

Answer 8

Beta-hexosaminidase A deficiency leads to accumulation of GM2 ganglioside

Question 9

Name the deficiency and accumulation seen in Gaucher disease.

Answer 9

Glucocerebrosidase (beta-glucosidase) deficiency leads to accumulation of glucocerebroside

Question 10

Name the deficiency and accumulation seen in Niemann-Pick disease.

Answer 10

Sphingomyelinase deficiency leads to accumulation of sphingomyelin

Question 11

Name the deficiency and accumulation seen in Krabbe disease.

Answer 11

Galactocerebrosidase deficiency leads to accumulation of galactocerebroside and psychosine.

Question 12

Name the deficiency and accumulation seen in Metachromatic leukodystrophy.

Answer 12

Arylsulfatase A deficiency leads to accumulation of cerebroside sulfate.

Question 13

Presentation - episodic peripheral neuropathy, angiokeratomas, and hypohidrosis (early) + late progressive renal failure and cardiovascular disease

Answer 13

Fabry disease

Question 14

Presentation - progressive neurodegeneration, developmental delay, “cherry-red” spot on macula; no hepatosplenomegaly

Answer 14

Tay-Sachs

Question 15

Presentation - Hepatosplenomegaly, pancytopenia, osteoporosis, avascular necrosis of the femur, bone crises

Answer 15

Gaucher disease

Question 16

Presentation - progressive neurodegeneration, hepatosplenomegaly, “cherry-red” spot on macula

Answer 16

Niemann-Pick disease

Question 17

Presentation - peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy

Answer 17

Krabbe disease

Question 18

Presentation - central and peripheral demyelination with ataxia (progressive neurodegeneration), peripheral neuropathy, dementia

Answer 18

Metachromatic leukodystrophy

Question 19

DDx - sphingolipidoses with “cherry-red” spot on macula

Answer 19

Tay-Sachs (NO hepatosplenomegaly)

Niemann-Pick (hepatosplenomegaly)

Question 20

Sphingolipidoses with osteoporosis, avascular necrosis of the femur, and/or bone crises

Answer 20

Gaucher disease (also, hepatosplenomegaly and pancytopenia)

Question 21

What is the triad seen in early Fabry disease?

Answer 21

1. Episodic peripheral neuropathy
2. Angiokeratomas
3. Hypohidrosis

Question 22

Which sphingolipidoses has cardiovascular and renal involvement?

Answer 22

Fabry disease

Question 23

Which sphingolipidoses presents with optic atrophy?

Answer 23

Krabbe disease (also, peripheral neuropathy, destruction of oligodendrocytes, developmental delay)

Question 24

Key histologic finding in Tay-Sachs disease?

Answer 24

Lysosomes with onion skin

Question 25

Compare histologic findings of Gaucher disease and Niemann-Pick disease.

Answer 25

Gaucher cells - lipid-laden macrophages resembling crumped paper

Niemann-Pick - lipid-laden foam cells