Wilson’s disease - liver disease

Wilson’s disease

Definition

Inherited disorder causing copper accumulation in the liver, brain, kidney, cornea and bone.

Prevalence

Rare; 1 in 50,000 of the population.

Age

May present at any age. Unusual before 5 years.

Sex

M = F

Aetiology

Inherited in an autosomal recessive manner. The mutation is in a copper-transport ATPase gene on chromosome 13.

Pathophysiology

In Wilson’s disease the mutation is thought to affect the excretion of copper from hepatic lysosomes into the bile. Excess copper in the hepatocytes causes lipid to collect in the cytoplasm. There is increasing inflammation and fibrosis and untreated, it progresses to cirrhosis.

Clinical features

Heterozygous individuals are asymptomatic and usually have a completely normal copper balance. In homozygotes, the condition may present with acute hepatitis or may remain clinically silent until cirrhosis is established or neurological symptoms develop including reduced performance at school, clumsiness or slurred speech. Kayser–Fleischer rings (green/brown rings around the edge of the cornea) are a late diagnostic sign, but are variably present.

Microscopy

Excess copper can be seen in the liver using special staining. It is ∼2–20 × normal, but this also occurs in chronic cholestatic disorders, such as primary biliary cirrhosis.

Investigations

Reduced serum copper and ceruloplasmin levels (not specific and 25% of patients will have normal levels). Urinary copper is high and increases markedly following a test dose of D-penicillamine. A slit-lamp examination of the eyes should be performed.

Management

D-penicillamine (a copper-chelating agent) depletes copper stores. Patients should avoid foods high in copper (chocolate, nuts and dried fruits). Siblings and children of affected individuals should be screened. If diagnosed and treated sufficiently early, there is some improvement in liver function and further deterioration is arrested.