Lysosomal Storage Diseases

Question 1

Fabry disease

What is the inheritance pattern? Deficient enzyme? Accumulated substrate? Findings?

Answer 1

Inheritance pattern: X-linked Recessive

Deficient enzyme: alpha-galactosidase A

Accumulated substrate: ceramide trihexosidase

Findings: Angiokeratomas (see image), peripheral neuropathy of hands and feet, cardiovascular and renal disease

Question 2

Gaucher disease

What is the inheritance pattern? Deficient enzyme? Accumulated substrate? Findings? Treatment?

Answer 2

Inheritance pattern: AR

Deficient enzyme: Glucocerebrosidase (beta-glucosidase)

Accumulated substrate: Glucocerebroside

Findings: HSM, pancytopenia, aspetic necrosis of femur, Gaucher cells (lipid-laden macrophages resemble tissue paper)

Treatment: recombinant glucocerebrosidase

Question 3

Niemann-Pick disease

What is the inheritance pattern, deficient enzyme, accumulated substrate, findings?

Answer 3

Inheritance pattern: AR, increased incidence in Ashkanazi Jews

Deficient enzyme: Sphingomyelinase

Accumulated substrate: sphingomyelin

Findings: HSM, progressive neurodegernation, foam cells, cherry-red spot on macula

Question 4

Tay-Sachs disease

What is the inerheitance pattern? Deficient enzyme? Accumulated substrate? Findings?

Answer 4

Inheritance pattern: AR, increased incidence in Ashkanazi Jews

Deficient enzyme: Hexosaminidase A “TAy-saX laX heXosaminidase A”

Accumulated substrate: GM2 ganglioside

Findings: progressive neurodegeneration, “cherry-red” spon on macula, “onion skin” lysosomes,

NO HSM (differentiates from Niemann-Pick)!

Question 5

Krabbe disease

Answer 5

Inheritance: AR

Deficient enzyme: galactocerebrosidase

Accumulated substrate: galactocerebroside, psychosine

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

Question 6

Metachromatic leukodystrophy

Answer 6

Inheritance: AR

Deficient enzyme: Arylsulfatase A

Accumulated substrate: Cerebroside sulfate

Findings: Central and peripheral demyelination with ataxia, dementia

Question 7

Hurler syndrome

Answer 7

Inheritance: AR

Deficient enzyme: alpha-L-iduronidase (mucopolysaccharidoses disease)

Accumulated substrate: Heparan sulfate, dermatan sulfate

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

Question 8

Hunter syndrome

Answer 8

Inheritance: XR

Deficient enzyme: Iduronate sulfatase

Accumulated substrate: heparan sulfate, dermatan sulfate

Findings: Mild Hurler syndrome + aggressive behavior, NO corneal clouding

Question 9

Which lysosomal storage diseases have hepatosplenomegaly?

Answer 9

Gaucher disease

Niemann-Pick disease

Hurler syndrome