Wilson’s disease

Abdul Waris Khan

Dept: Internal medicine

SOEPEL

Definition

• Wilson’s disease is a very rare inborn error of copper metabolism that results in copper deposition in various organs, including the liver, the basal ganglia of the brain and the cornea. It is potentially treatable.

Aetiology

• It is an autosomal recessive disorder with a molecular defect within a copper-transporting ATPase encoded by a gene (ATP7B) located on chromosome 13. The most frequent mutation being “His1069 Gly (H1069Q)” is seen in Caucasian patients and is rare in India and Asia.

• Dietary copper is normally absorbed from the stomach and upper small intestine. It is transported to the liver loosely bound to albumin. Here it is incorporated into apocaeruloplasmin forming caeruloplasmin, a glycoprotein synthesized in the liver, and secreted into the blood. The remaining copper is normally excreted in the bile and excreted in faeces.

Clinical features

• Children usually present with hepatic problems.

• Young adults have more neurological problems, such as tremor, dysarthria, involuntary movements and eventually dementia.

• The liver disease varies from episodes of acute hepatitis, especially in children, which can go on to fulminant hepatic failure, to chronic hepatitis or cirrhosis.

• A specific sign is the Kayser–Fleischer ring, which is due to copper deposition in Descemet’s membrane in the cornea. It appears as a greenish brown pigment at the corneoscleral junction and frequently requires slit-lamp examination for identification.

• It may be absent in young children.

Investigation

• Serum copper and caeruloplasmin are usually reduced but can be normal.

• Urinary copper is usually increased 100–1000 μg in 24 hours (1.6–16 μmol); normal levels < 40 μg (0.6 μmol).

• Liver biopsy. The diagnosis depends on measurement of the amount of copper in the liver (> 250 μg/g dry weight), although high levels of copper are also found in the liver in chronic cholestasis.

• Haemolysis and anaemia may be present.

• Genetic analysis is limited but selected exons are screened according to population group.

Treatment

• Lifetime treatment with penicillamine, 1–1.5 g daily.

• Urine copper levels should be monitored and the drug dose adjusted downwards after 2–3 years.

• Serious side-effects of the drug occur in 10% and include skin rashes, leucopenia, skin changes and renal damage.

• Trientine (1.2–1.8 g/day) and zinc acetate (150 mg/day) have been used as maintenance therapy and for asymptomatic cases.

• All siblings and children of patients should be screened (ATP7B mutation analysis is useful) and treatment given even in the asymptomatic if there is evidence of copper accumulation.

Prognosis

• Early diagnosis and effective treatment have improved the outlook.

• Neurological damage is, however, permanent.

• Ful-minant hepatic failure or decompensated cirrhosis should be treated by liver transplantation.

Referenes

• Kumar and Clark clinical medicine 7th edition