Lysosomal Storage Diseases

Question 1

Fabry’s disease

Answer 1

alpha-galactosidase A deficiency –> ceramide trihexoside accumulates
X-linked Recessive
Peripheral neuropathy of hands/feet
Angiokeratomas- corneal changes (whorl-like dystrophy)
Cardiovascular/renal disease– TIA’s, stroke, MI

Question 2

Gaucher’s disease

Answer 2

Most common
Glucocerebrosidase deficiency–> glucocerebroside builds up
Autosomal recessive
Hepatosplenomegaly–> pancytopenia/thrombocytopenia
Aseptic necrosis of femur, bone crises
Gaucher’s cells (macrophages that look like tissue paper)
Increased risk in Ashkenazic jews

Question 3

Neimann-Pick disease

Answer 3

Sphingomyelinase deficiency–> sphingomyelin builds up
Autosomal Recessive
Progressive neurodegeneration
Hepatosplenomegaly (vs. Tay-sachs)
Cherry-red spot on macula
Foam cells– “All those ‘sphoam’ cells will fill the liver/spleen”

Question 4

Tay-Sachs disease

Answer 4

Hexosaminidase A deficiency–> GM2 ganglioside build up
Autosomal recessive
Progressive neurodegeneration
*Developmental delay
Cherry-red spot on macula
*Lysosomes with onion skin
*No hepatosplenomegaly (vs. Neimann-Pick)
Increased risk in Ashkenazic Jews– presents early < 1yo

Question 5

Krabbe’s disease

Answer 5

Galactocerebrosidase deficiency–> galactocerebroside build up
Autosomal recessive
Peripheral neuropathy, developmental delay
*Optic atrophy
*Globoid cells

Question 6

Metachromatic leukodystrophy

Answer 6

Arylsulfatase A deficiency–> Cerebroside sulfate build up
Autosomal recessive
Central and peripheral demyelination with ataxia, dementia
Late infantile onset, death at 5-10 yo

Question 7

Hurler’s syndrome

Answer 7

A mucopolysaccharidoses
alpha-L-iduronidase deficiency –> Heparan/dermatan sulfate build up
Developmental delay
Gargoylism = short nose, flat face, prominent forehead, large head
Airway obstruction, corneal clouding, diarrhea, loose stools
Hepatosplenomegaly- umbilical/inguinal hernias often 1st sign

Question 8

Hunter’s syndrome

Answer 8

One of mucopolysaccharidoses
Iduronate sulfatase deficiency--> heparan/dermatan sulfate build up
**X-linked recessive
Mild Hurler's + AGGRESSIVE BEHAVIOR
*No corneal clouding