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Section XIX - Lysosomal Storage Diseases

I. Overview
A. Lysosomes breakdown obsolete components of
the cell.
B. Lysosomal storage diseases are caused by an
absence of lysosomal enzymes that metabolize
sphingolipids.
C. Sphingolipids are associated with nerve tissue.

II. Lysosomal storage diseases (Table 2.5.3)

Accumulated
Disease Deficient Enzyme Findings Inheritance
Substrate
-Palm and sole
neuropathy
Fabry disease -↓ autonomics
Ceramide X-linked
α-galactosidase A (sweat)
trihexoside recessive
“Fa - br - A” -Renal and CV failure
in adulthood
-Angiokeratoma
Niemann-Pick
disease -Weakness
-Cherry-red spot Autosomal
Sphingomyelinase Sphingomyelin
“No man picks -Hepatosplenomegaly recessive
his nose with his -Foam cells
sphinger”
Tay-Sachs disease -Weakness
-Cherry-red spot Autosomal
Hexosaminidase A GM2 ganglioside
“Tay-SaX lacks -Lysosomes with recessive
hexosaMinidase” onion skin
-Bone disease
Gaucher disease
-Lipid-laden Autosomal
Glucocerebrosidase Glucocerebroside
macrophages recessive
“GaUcher”
-Pancytopenia
-Weakness
Autosomal
Krabbe disease Galactocerebrosidase Galactocerebroside -Vision problems (no
recessive
cherry-red spot)
-Weakness
Metachromatic Autosomal
Arylsulfatase A Cerebroside sulfate -Dementia
leukodystrophy recessive
-Neuropathy

Table 2.5.3 - Lysosomal storage diseases

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REVIEW QUESTIONS ?
1. A 20-year-old male presents to the physician
for recent onset polyuria and polydipsia. Labs
are significant for proteinuria and an elevated
creatinine. Further investigation reveals a
deficiency of an enzyme normally present
in lysosomes. What other symptoms would
likely accompany the disorder described in this
vignette?

• Polyuria, polydipsia, proteinuria, and an

elevated creatinine → renal failure
• Fabry disease is the only lysosomal storage
disease that results in renal failure
• Other symptoms of Fabry disease include
palm and sole neuropathy, decreased
Normal retina sweat, cardiovascular failure, and angio-
keratomas

2. A 16-month-old boy is brought to the physician

for developmental delay. His parents are a
young Ashkenazi Jewish couple who state that
he is still unable to walk or crawl. Physical
exam reveals hypotonia, hepatosplenomegaly,
and a cherry-red spot on fundoscopic exam. A
deficiency of what enzyme is most likely the
cause of this patient’s disease?

• Weakness, hepatosplenomegaly, and a

cherry-red spot → Niemann-Pick disease →
deficiency of sphingomyelinase

Cherry-red spot