Lysosomal Storage Diseases

Question 1

Fabry’s Disease (sphingolipidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 1

1. Peripheral neuropathy of hands/feet; angiokeratomas; cardiovascular/renal disease
2. alpha-galactosidase A
3. Ceramide trihexoside
4. X-linked recessive

Question 2

Gaucher’s Disease (sphingolipidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 2

Most common

1. Hepatosplenomegaly; aseptic necrosis of femur; bone crises; Gaucher’s cells (macrophages that look like crumpled tissue paper)
2. Glucocerebrocidase
3. Glucocerebroside
4. Autosomal recessive

Question 3

Niemann-Pick Disease (sphingolipidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 3

1. Progressive neurodegeneration; hepatosplenomegaly; cherry-red spot on macula; foam cells
2. Sphingomyelinase
3. Sphingomyelin
4. Autosomal recessive

Question 4

Tay-Sachs Disease (sphingolipidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 4

1. Progressive neurodegeneration; developmental delay; cherry-red spot on macula; lysosomes with onion skin; no hepatosplenomegally (vs. Niemann-Pick)
2. Hexosaminidase A
3. GM2 ganglioside
4. Autosomal recessive

Question 5

Krabbe’s Disease (sphingolipidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 5

1. Peripheral neuropathy; developmental delay; optic atrophy; globoid cells
2. Galactocerebrosidase
3. Galactocerebroside
4. Autosomal recessive

Question 6

Metachromatic Leukodystrophy (sphingolipidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 6

1. Central and peripheral demyelination with ataxia; dementia
2. Arylsulfatase A
3. Cerebroside sulfate
4. Autosomal recessive

Question 7

Hurler’s Syndrome (mucopolysaccharidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 7

1. Developmental delay; gargoylism; airway obstruction; corneal clouding; hepatosplenomegaly
2. alpha-L-iduronidase
3. Heparan sulfate, dermatan sulfate
4. Autosomal recessive

Question 8

Hunter’s Syndrome (mucopolysaccharidoses)

1. Findings
2. Deficient Enzyme
3. Accumulated Substrate
4. Inheritance

Answer 8

1. Mild Hurler’s + aggressive behavior; no corneal clouding (if you’re going to be a hunter, you need to be aggressive and able to see)
2. Iduronate sulfatase
3. Heparan sulfate, dermatan sulfate
4. X-linked recessive

Question 9

Lysosomal Storage Diseases

Answer 9

• 2 broad classes: sphingolipidoses, mucopolysaccharidoses
• Each is caused by deficiency of a lysosomal enzyme
• Results in accumulation of abnormal metabolic products

Question 10

Lysosomal Storage Disease pnemonics and factoids

Answer 10

1. No man picks (Niemann-Pick) his nose with his sphinger (sphingomyelinase)
2. Tay-SaX lacks heXosaminidase
3. Hunters see clearly (no corneal clouding) and aim for the X (X-linked recessive)
4. Increased incidence of Tay-Sachs, Niemann-Pick, and some forms of Gaucher’s disease in Ashkenazi Jews