Lysosomal Storage Disorders Flashcards
1
Q
describe Hurler syndrome
A
- enzyme deficient: iduronidase
- substrates accumulating: dermatan sulfate and heparan sulfate
- urine is positive for GAGs
- enzyme replacement therapy with iduronidase has been successful
2
Q
describe Hunter syndrome
A
X-linked recessive
- enzyme deficient: iduronate sulfatase
- coarse facial features, hepatosplenmegaly, mild to moderate dev. delay, NO CORNEAL CLOUDING
- hematopoietic stem cell therapy
3
Q
what are 2 differences between Hurler and Hunter syndrome
A
- Hurler = autosomal recessive, Hunter = X-linked
- Hurler = corneal clouding, Hunter = NO CORNEAL CLOUDING
4
Q
describe Tay-Sachs
A
- deficient enzyme: B-hexosaminidase A
- accumulating substrate: ganglioside (GM2)
- progressive neurodegeneration, development milestone delay, often regression
- generally fatal by 2-6 years
5
Q
what are clinical features of Tay-Sachs
A
- EM diagram shows “onion-shell” inclusion; the lysosome looks like an onion shell
- cherry-red spot on macula caused by GM2 accumulation
6
Q
describe Gaucher disease
A
most common lysosomal storage disorder
- deficienct enzyme: B-glucosidase
- accumulating substrate: glucosyl ceramide (glucocerebroside)
- macrophages engorged with glucocerebrosides
- adult form (most common) sho no neurological damage but marked hepatosplenomegaly and osteoporosis of long bone
7
Q
describe the cell appearance in Gaucher disease
A
- crumpled tissue paper appearance of cytoplasm that is caused by enlarged, elongated lysosomes filled with glucocerebroside
- distal femur in the shape of an Erlenmeyer flask
8
Q
describe Fabry disease
A
X-linked recessive disorder
- deficient enzyme: α-galactosidase
- accumulating substrate: globoside (aka ceremide trihexoside)
- peripheral neuropathy, acroparesthesias (tingling and burning of extremities)
9
Q
describe clinical features of Fabry disease
A
- globoside accumulates in the blood vessels of skin, kidneys, nerves and heart
- carrier females can show mild clinical features (skewed X-inactivation)
10
Q
describe Niemann-Pick disease
A
- deficient enzyme: sphingomyelinase
- accumulating substrate: sphingomyelin (sphingophospholipid)
- accumulation of sphingomyelin in the neuronal tissues
- Type A is a severe infantile form
- cherry red spot in macula
- similar to Tay-Sachs
- cherry red spot in macula
- Type B appears later in childhood, presents with hepatosplenomegaly
11
Q
describe cell appearnce in Niemann-Pick disease
A
- deficiency of sphingomyelinase causes lipid droplet accumulation; “foamy cell” appearance
12
Q
describe metachromatic leukodystrophy
A
- deficient enzyme: aryl sulfatase A
- accumulating substrate: sulfatide (rich in neurons)
- progressive paralysis and demyelination
13
Q
overview of lysosomal storage disorders
A
14
Q
describe Pompe disease
A
- a small amount of cellular glycogen is degraded by lysosomal acid maltase (1->4 glucosidase)
- generalized accumulation of glycogen in heart, muscle, kidney and liver as vacuoles in the lysosomes (glycogen storage disorder type II)
- enzyme replacement therapy has been successful
15
Q
describe normal trafficking of enzymes to the lysosomes
A
- enzymes synthesized in the ER are transported to the Golgi
- in the Golgi, there is phosphorylation of mannose to form mannose-6-phosphate
- enzymes that have a mannose-6-P are transported to the lysosomes
- enzymes without the M6P are secreted by the cell
- N-acetylglucosamine-1-phosphate transferase
