Lysosomal Storage Disorders

Question 1

Hurler Syndrome

Answer 1

deficient- a-L-Iduronidase
accumulation- Dermatan sulfate & heparan sulfate

urine postive for GAGS
affects degradation of dermatan/heparin sulfate (deposition in coronary arteries can lead to death)

-corneal clouding, dwarfing, coarse facial features, airway obstruction, hearing loss

iduronidase (enzyme replacement therapy)

Question 2

Hunter Syndrome

Answer 2

deficient- Iduronate sulfatase

X-linked recessive (predominatly males)

milder form
affects degradation of dermatan/heparin sulfate

• coarse facial features, hepatosplenomegaly, developmental delay
• NO CORNEAL CLOUDING

enzyme replacement therapy

Question 3

Sphingolipidoses

Answer 3

complex lipids (contain sphingosine as alcohol instead of glycerol) 
sphingosine + fatty acid = ceramide 

two classes

• glycosphingolipids/glycolipid -contain carbohydrate moiety linked to ceramide
• sphingophospholipids contain phosphoryl choline moiety linked to ceramide (sphingomyelin)

Question 4

Tay-Sachs disease

Answer 4

deficient- B-Hexosaminidase A

accumulation of Ganglioside (Gm2) (ganliosidosis)

• neurodegeneration after 3-6 months, blindess
• cherry read spot on macula
• onion shell incluisons in lysosomes

fatal by 2-6 years

• carriers (heterozygotes) 1 copy of mutant gene, 1 normal gene
• can be detected via enzyme assays
• 50% hexosaminidase activity (phenotypically normal)

Question 5

Gaucher disease

Answer 5

most common

deficient- B-Glucosidase
accumulation- Glucosyl ceramide (glucocerebroside)

macrophages engorged with glucocerebrosides

adult form (most common)

• no neurological damage
• marked hepatosplenomegaly
• osteoperosis of long bones “erlenmeyer flask femur”
• “bone crisis”

enzyme replacement therapy

Question 6

Fabry disease

Answer 6

deficient- a-Galactosidase
accumulating- Globoside (ceramide trihexoside)

• peripheral neuropathy (tingling/burning of extremities)
• “acroparesthesias”

globosdie accumulates in blood vessels of skin, kidneys, nerves, and heart
children may have fatal complicaitons (kidney damage, heart attack, stroke)

carrier females can show mild clinical features

Question 7

Niemann-Pick disease

Answer 7

deficient- Sphingomyelinase
accumulating- Sphingomyelin (sphingophospholipid)

accumulaiton of sphingomyelin in neuronal tissues

Type A
severe infantile forme (fatal by 2-3 years)
cherry-red spot on macula (blindness)

Type B
later in childhood
presents with hepatosplenomegaly

common feature for both types- lipid droplet accumulaiton “foamy cell appearence)

Question 8

Metachromatic leukodystrophy

Answer 8

deficient- Aryl Sulfatase A
accumulating- Sulfatide (rich in neurons)

-progressive paralysis and demyelination

Question 9

Pompe disease

Answer 9

deficient- lysosomal acid maltase (1>4 glucosidase)

accumulation of glycogen in heart (cardiac failure), muslce (myophathy), kidney, liver (hepatocellular damage)
(vacuoles in lysosomes) GSD type III

enzyme replacement therapy

Question 10

I-cell disease (inclusion cell disease)

Answer 10

detect in trafficking enzymes to lysosomes
fails to add mannose-6-P marker

enzymes secreted into blood stream (high concentration of lysosomal enzymes in blood)

deficiency of many lysosomal enzymes
accumulation of GAGS and sphingolipids in lysosomes

presence of intracytoplasmic inclusions in fibroblasts
“inclusion cells” “I-cells”

similar clinical manifestations of Hurler’s yet more severe an onset at earlier age