Lysosomal Storage Disorders

Question 1

Tay-Sachs disease

Answer 1

enzyme: heXosaminidase A; accumulates: GM2 ganglioside; progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosomes with onion skin, no HSM

Question 2

Fabry disease

Answer 2

enzyme: alpha-galactosidase A; accumulates: ceramide trihexoside; X-linked; early: triad of episodic peripheral neuropathy, angiokeratomas, hypohidrosis; late: progressive renal failure, CV disease

Question 3

Metachromatic leukodystrophy

Answer 3

enzyme: arylsulfatase A; accumulates: cerebroside sulfate; central and peripheral demyelination with ataxia, dementia

Question 4

Krabbe disease

Answer 4

enzyme: galactocerebrosidase; accumulates: galactocerebroside, psychosine; peripheral neuropathy, destruction of oligodendrocytes, developmental delay, optic atrophy, globoid cells

Question 5

Gaucher disease

Answer 5

enzyme: glucocerebrosidase; accumulates: glucocerebroside; most common**;; HSM, pancytopenia, osteoporosis, avascular necrosis of femur, lipid-laden macrophages resembling crumbled tissue paper

Question 6

Niemann-Pick disease

Answer 6

enzyme: sphingomyelinase; accumulates: sphingomyelin; progressive neurodegeneration, HSM, foam cells, cherry red spot on macula

Question 7

Hurler syndrome

Answer 7

enzyme: alpha-L-iduronidase; accumulates: heparan sulfate, dermatan sulfate; developmental delay, airway obstruction, gargoylism, corneal clouding, HSM

Question 8

Hunter syndrome

Answer 8

enzyme: iduronate sulfatase; accumulates: heparan sulfate, dermatan sulfate, X-linked, mild hurler + aggressive behavior , no corneal clouding

Question 9

General feature of the mucopolysaccharidoses?

Answer 9

Coarse facial features in Hunters and Hurlers

Question 10

Important diagnostic tool for Hurlers and Hunter?

Answer 10

oligosaccharides in urine (due to incomplete lysosomal degradation of GAGs)

Question 11

Treatment for Gaucher disease

Answer 11

recombinant glucocerebrosidase in type I Gaucher

Question 12

I cell disease

Answer 12

An inherited LSD

Failure of golgi to phosphorylate mannose residues–>proteins are secreted rather than delivered to lysosomes
Deficiency in N-acetylglucosaminyl-1-phosphotransferase

Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes

Looks kind of like Hurler but has the restricted joint movements