PATH - Lysosomal storage diseases

Question 1

Fabry disease

Answer 1

Sphingolipidoses

XR

DEFICIENT ENZYME
*α-galactosidase A

aCCuMulaTED SuBSTRaTE
*Ceramide trihexoside

Early: Triad of episodic peripheral neuropathy, angiokeratomas, hypohidrosis.

Late: progressive renal
failure, cardiovascular disease

Question 2

Gaucher disease

Answer 2

Sphingolipidoses

AR

DEFICIENT ENZYME
*Glucocerebrosidase
(β-glucosidase); treat with recombinant glucocerebrosidase

aCCuMulaTED SuBSTRaTE
Glucocerebroside

Most common.

Hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crises, *Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper).

Question 3

Niemann-Pick disease

Answer 3

Sphingolipidoses

AR

DEFICIENT ENZYME
Sphingomyelinase

aCCuMulaTED SuBSTRaTE
Sphingomyelin

Progressive neurodegeneration,
hepatosplenomegaly, *foam cells (lipid-laden macrophages), *“cherry-red” spot on macula

Question 4

Tay-Sachs disease

Answer 4

Sphingolipidoses

AR

DEFICIENT ENZYME
Hexosaminidase A

aCCuMulaTED SuBSTRaTE
GM2 ganglioside

Progressive neurodegeneration,
developmental delay, *“cherry-red” spot on macula, lysosomes with onion skin, *no hepatosplenomegaly
(vs Niemann-Pick).

Question 5

Krabbe disease

Answer 5

Sphingolipidoses

AR

DEFICIENT ENZYME
Galactocerebrosidase

aCCuMulaTED SuBSTRaTE
Galactocerebroside,
psychosine

Peripheral neuropathy, developmental delay, optic atrophy, globoid cells.

Question 6

Metachromatic leukodystrophy

Answer 6

Sphingolipidoses

AR

DEFICIENT ENZYME
Arylsulfatase A

aCCuMulaTED SuBSTRaTE
Cerebroside sulfate

Central and peripheral demyelination with ataxia, dementia.

Question 7

Hurler syndrome

Answer 7

Mucopolysaccharidoses

AR

DEFICIENT ENZYME
α-l-iduronidase

aCCuMulaTED SuBSTRaTE
Heparan sulfate, derma tan sulfate

Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly

Question 8

Hunter syndrome

Answer 8

Mucopolysaccharidoses

XR

DEFICIENT ENZYME
Iduronate sulfates

aCCuMulaTED SuBSTRaTE
Heparan sulfate, derma tan sulfate

Mild Hurler + aggressive behavior, *no corneal clouding