Lysosomal Storage Diseases: Sphingolipidoses and Mucopolysaccharidoses

Question 1

What disease interferes with the metabolism of ceramide trihexoside? Enzyme deficiency? 3 main Sx?

Answer 1

Fabry’s disease, a deficiency of alpha-galactosidase A.
Sx: hypohydrosis (adiaphoresis), angiokeratomas, and acroparesthesia. Risk of renal failure, htn, cardiomyopathy, and ocular manifestations.

Question 2

hepatosplenomegaly, aseptic necrosis of the femur, bone crises, macrophages that look like crumpled tissue paper. Disease? Etiology?

Answer 2

Gaucher’s disease. Glucocerebrosidase deficiency.

Question 3

What does a deficiency of sphingomyelinase cause?

Answer 3

Neimann-Pick disease: progressive neurodegeneration (loss of previously acquired motor skills), hepatosplenomegaly, cherry red spot on macula, “foamy histiocytes”. Death before age 3.

Question 4

How is Tay-Sachs different from Neimann-Pick?

Answer 4

hexosaminidase A, GM2 ganglioside.

no hepatosplenomegaly.

Question 5

Which sphingolipidosis is X-linked recessive?

Which mucopolysaccharidosis?

Answer 5

Fabry’s disease.

Hunter’s syndrome.

Question 6

Which sphingolipidosis causes a buildup of galactocerebroside?

Answer 6

Krabbe’s disease

Question 7

Causes central and peripheral demyelination with ataxia and dementia. Deficient enzyme and accumulated substrate?

Answer 7

Metachromatic leukodystrophy.

Aryl sulfatase A deficiency causes a buildup of cerebroside sulfate.

Question 8

Hurler’s syndrome is due to a defect of alpha-L-iduronidase, and a subsequent accumulation of heparan sulfate and dermatan sulfate. What are the Sx?

Answer 8

Dev. delay, “gargoylism”, airway obstruction, corneal clouding, and hepatosplenomegaly. Death before 10 is frequent.

Question 9

How is Hunter’s syndrome different from Hurler’s?

Answer 9

XR, enzyme deficiency is iduronate sulfatase.

Sx: milder + aggressive behavior and no corneal clouding.