Wilson's disease

Question 1

Pathophysiology of Wilson’s disease?

Answer 1

AR defect of ATP7B2, involved in the binding and production of ceruloplasmin

Question 2

Diagnosis of Wilson’s disease

Answer 2

Gold standard is liver copper on biopsy, with high urinary copper post penicillamine

Question 3

Clinical features of Wilson’s disease

Answer 3

Brain deposition (basal ganglia)
Descemet's membrane (Kayser-Fleischer rings)
Acute hepatitis --> cirrhosis
Hepatosplenomegaly
Renal disease
Haemolytic disease (free radical damage)

Question 4

Laboratory investigations found in Wilson’s disease

Answer 4

Reduced cerulosplasmin
Increased FREE copper
Increased urine copper
AST:ALT (ratio >4)
ALP is falsely low (zinc dependent enzyme displaced by copper)

Question 5

Treatment of Wilson’s disease

Answer 5

Penicillamine or trientine (chelation)
Typical side effect is peripheral neuropathy of B6 deficiency (pyridoxine)
Zinc (outbinds copper, causing it to be excreted in urine)

Question 6

Menke’s disease

Answer 6

Opposite of Wilson’s disease. X linked disorder of copper deficiency due to mutation in ATP7A.
Characterised by kinky hair, growth failure and hypotonia + hypothermia, with progressive cerebral infarction, leading to seizures and neurological impairment. Brittle bones are often seen on xray. Associated with death in early childhood.