Wilson disease
Wilson disease is an autosomal recessive disorder of the ATP7B copper-transporting ATPase causing toxic copper accumulation in the liver, brain, and cornea, presenting with hepatic and/or neuropsychiatric disease usually before age 40; diagnosis rests on ceruloplasmin, urinary copper, and Kayser-Fleischer rings, and lifelong treatment is chelation with penicillamine or trientine, or zinc, unless liver transplant is required.
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What this article covers
- Overview
Definition: Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder of copper metabolism in which a defective hepatocyte copper-transporting ATPase causes toxic copper…
- Epidemiology
Onset typically before age 40, with hepatic presentations skewing toward children and adolescents and neurologic presentations skewing toward older patients within that range.
- Risk factors
Family history of Wilson disease, especially an affected sibling, given autosomal recessive inheritance.
- Pathophysiology
Mutation of the copper-transporting ATPase gene (ATP7B) impairs two linked hepatocyte functions: incorporation of copper into apoceruloplasmin to form ceruloplasmin, and biliary excretion of excess…
- Clinical features
Hepatic manifestations, more common in younger patients: range from asymptomatic transaminase elevation and chronic hepatitis to steatohepatitis, insidiously developing cirrhosis, and acute liver…
- Differential diagnosis
Hemochromatosis: another metal storage disease presenting with cirrhosis, but with iron overload rather than copper overload, elevated serum iron and ferritin with markedly elevated transferrin…
- Diagnosis
The diagnosis is confirmed by a low serum ceruloplasmin level (typically below 20 mg/dL) together with an increased urinary or hepatic copper concentration (24-hour urinary copper typically above 100…
- Management
First, confirm the diagnosis and start lifelong copper-lowering treatment promptly, since Wilson disease is progressive and largely reversible if started before advanced organ damage occurs.
- Complications
Cirrhosis and its sequelae, including portal hypertension, ascites, and variceal bleeding, in patients with unrecognized or inadequately treated hepatic disease.
- Prognosis
Excellent prognosis with early diagnosis and adherence to lifelong therapy, particularly when treatment is started before significant hepatic or neurologic damage has occurred.
- Prevention
Screen all first-degree relatives, especially siblings, of every confirmed patient for Wilson disease with serum ceruloplasmin (looking for a value below 20 mg/dL), liver function testing, and…
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