Inherited Metabolic Disorders

Question 1

Glycogen Storage Diseases

Answer 1

Glycogen storage disease:

Von Gierke’s disease (type I):
Deficienct Enzyme = Glucose-6-phosphatase
- Hepatic glycogen accumulation.
- Key features include hypoglycaemia, lactic acidosis, hepatomegaly

Pompe’s disease (type II)
Deficient Enzyme = Lysosomal alpha-1,4-glucosidase
- Cardiac, hepatic and muscle glycogen accumulation.
- Key features include cardiomegaly

Cori disease (type III)
Deficient Enzyme = Alpha-1,6-glucosidase (debranching enzyme)
- Hepatic, cardiac glycogen accumulation
- Key features include muscle hypotonia

McArdle’s disease (type V)
Deficient Enzyme = Glycogen phosphorylase - Skeletal muscle glycogen accumulation.
- Key features include myalgia, myoglobulinaemia with exercise

Question 2

Lysosomal Storage Diseases

Answer 2

Lysosomal Storage Diseases

Gaucher’s disease
Defect = Beta-glucocerebrosidase
- Most common lipid storage disorder resulting in accumulation of glucocerebrosidase in the brain, liver and spleen.
- Key features include hepatosplenomegaly, aseptic necrosis of the femur

Tay-Sachs disease
Defect = Hexosaminidase A
- Accumulation of GM2 ganglioside within lysosomes.
- Key features include developmental delay, cherry red spot on the macula, liver and spleen normal size (cf. Riemann-Pick)

Niemann-Pick disease
Defect = Sphingomyelinase
- Key features include hepatosplenomegaly, cherry red spot on the macula

Fabry disease
Defect= Alpha-galactosidase-A
- Accumulation of ceramide trihexoside.
- Key features include angiokeratomas, peripheral neuropathy of extemeties, renal failure

Krabbe’s Disease
Defect = Galactocerebrosidase
- Key features include peripheral neuropathy, optic atrophy, globoid cells

Metachromatic leukodystrophy
Defect = Arylsulfatase A
- Demyelination of the central and peripheral nervous system

Question 3

Mucopolysaccharidoses

Answer 3

Mucopolysaccharidoses

Hurler syndrome (type I)
Defect = Alpha-1-iduronidase
- Accumulation of glycosaminoglycans (heparan and dermatan sulfate).
- Key features include gargoylism, hepatosplenomegaly, corneal clouding

Hunter syndrome (type II)	
Defect = Iduronate sulfatase	
- Accumulation of glycosaminoglycans (heparan and dermatan sulfate). 
- Key features include coarse facial features, behavioural problems/learning difficulties short stature, no corneal clouding