Lysosomal Storage Diseases

Question 1

Hurler Syndrome

Answer 1

mucopolysaccharideosis

Iduronidase Deficiency

Accumulation of Dermatan sulfate and heparan sulfate

Coarse facial features, hepatosplenomegaly, mild to moderate mental retardation, Corneal clouding

Question 2

Hunter Syndrome

Answer 2

mucopolysaccharideosis

Iduronate Sulfatase Deficiency

Accumulation of Dermatan sulfate and heparan sulfate

X-linked recessive disorder

Coarse facial features, hepatosplenomegaly, mild to moderate mental retardation, NO Corneal clouding

Question 3

Tay-Sachs disease

Answer 3

Deficient enzyme: Beta-Hexosaminidase A

Accumulating substrate: Ganglioside (GM2). (Also known as gangliosidosis)

• Progressive neurodegeneration after the age of 3-6 months, blindness
• Developmental milestone delay (child not able to sit or stand in the later stages)
• Generally fatal by 2-6 years

Question 4

Fabry Disease

Answer 4

Deficient enzyme: Alpha-Galactosidase

Accumulating substrate: Globoside (aka ceramide trihexoside)

Peripheral neuropathy (tingling of extremities)
Globoside accumulates in vessels of the skin, kidneys, nerves, and heart. 

X-Linked recessive disorder.

Question 5

Gaucher Disease

Answer 5

Deficient enzyme: β-Glucosidase

Accumulating substrate: Glucosylceramide(aka glucocerebroside)

Macrophages engorged with glucocerebrosides

Adult form (most common) shows no neurological damage but marked hepatosplenomegaly and osteoporosis of long bones

Crumpled Tissue paper appearance of the cytoplasm.

Most Common Lysosomal Storage Disorder

Question 6

Niemann-Pick Disease

Answer 6

Deficient enzyme: Sphingomyelinase

Accumulating substrate: Sphingomyelin (sphingophospholipid)

Accumulation of sphingomyelin in the neuronal tissues

Type A is a severe infantile form –fatal by 2-3 years

Type B appears later in childhood, presents with
hepatosplenomegaly

Cherry-red spot in macula on retinal examination

Foamy appearing cells containing sphingomyelin

Question 7

Metachromatic leukodystrophy

Answer 7

Deficient enzyme: Aryl SulfataseA

Accumulating substrate: Sulfatide

Progressive paralysis and demyelination

Question 8

Pompe Disease

Answer 8

Glycogen storage disorder Type II

Deficient Enzyme: Lysosomal Acid Maltase

Accumulation of glycogen in heart, muscles, kidneys, and liver.

Question 9

I-Cell Disease

Answer 9

Inclusion-Cell Disease

The Golgi fails to add the mannose-6-P marker to the enzymes destined for the lysosomes

Presence of high concentration of lysosomal enzymes in the blood

Deficiency of many lysosomal enzymes, and accumulation of glycosaminoglycans and sphingolipids in the lysosomes

intracytoplasmic inclusions in the fibroblasts of patients

Manifestations similar to Hurler syndrome, but more severe and an earlier age of onset

Question 10

Functions of Lysosomes

Answer 10

Normal degradation of cellular components
Digestion of phagocytosed materials
Digestion of material from receptor mediated endocytosis (LDL receptors)
Autophagy

May play a role in extracellular digestion