Lysosomal Storage Disease

Question 0

Gaucher disease

Answer 0

Findings: hepatosplenomegaly, pancytopenia, bone necrosis/crises, gay her cells (lipid-laden macros)

Deficient enzyme: glucocerebrosidase (beta-glucosidase)

Accumulated substrate: glucocerebroside

Inheritance: AR

Question 1

Fabry disease

Answer 1

Findings: peripheral neuropathy, angikeratomas, CVD, CRD

Deficient enzyme: Alpha-galactosidase A

Accumulated substrate: ceramide trihexoside

Inheritance: XR

Question 2

Niemann-Pick disease

Answer 2

Findings:Progressive neurodegeneration, hepatosplenomegaly, “cherry-red” spot on macula, foam cells

Deficient enzyme: sphingomyelinase

Accumulated substrate: sphingomyelin

Inheritance: AR

Question 3

Tay-Sachs disease

Answer 3

Findings: Progressive neurodegeneration, “cherry-red” spot on macula, lysosomes with onion skin

Deficient enzyme: hexosaminidase A

Accumulated substrate: GM2
ganglioside

Inheritance: AR

Question 4

Krabbe disease

Answer 4

Findings: peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Deficient enzyme: galactocerebrosidase

Accumulated substrate: galactocerebroside

Inheritance: AR

Question 5

Metachromatic leukodystrophy

Answer 5

Findings: central and peripheral demyelination with ataxia, dementia

Deficient enzyme: arylsulfatase A

Accumulated substrate: cerebroside sulfate

Inheritance: AR

Question 6

Hurler syndrome

Answer 6

Findings: developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly

Deficient enzyme: alpha-L-iduronidase

Accumulated substrate: heparin sulfate, dermatin sulfate

Inheritance: AR

Question 7

Hunter syndrome

Answer 7

Findings: developmental delay, gargoylism, airway obstruction, hepatosplenomegaly (all milder than hurler) + aggressive behavior

Deficient enzyme: iduronate sulfatase

Accumulated substrate: heparin sulfate, dermatin sulfate

Inheritance: AR