This is an autosomal recessive disorder of copper metabolism secondary to a genetic defect located on chromosome 13. It presents itself as an accumulation of toxic levels of copper in many tissues. Copper accumulation typically occurs in the liver, brain, and eyes, hence the designation hepatolenticular degeneration. The prevalence of this disease is one in 30,000 persons. The frequency of heterozygous carriers is one in 90 persons.

Normally, one-half of dietary copper is absorbed. Excretion of copper occurs mainly through biliary excretion with only negligible amounts of urinary excretion. In Wilsons disease, there is a defect in biliary copper excretion; however, the exact mechanism is currently unknown.

Symptoms of this disease are related to hepatic and neurologic toxicity plus the associated hemolytic anemia. Neurologic symptoms include the presence of Kayser-Fleischer corneal rings, tremor, dysarthria, sialorrhea, incoordination, ataxia, oropharyngeal dysphagia, and grimacing. These symptoms will progress to include dystonia, spasticity, rigidity, and seizures if therapy is not offered. Cognitive and sensory function is usually not affected. Hepatic manifestations include hepatic insufficiency with portal hypertension and resultant splenomegaly and/or ascites. Esophageal varices are an uncommon complication. Many patients present with psychiatric abnormalities. Coombs negative intravascular hemolysis is often noted with this disease. In children hepatic symptoms predominate whereas, in adolescents and adults, neuropsychiatric symptoms predominate.

When screening for this disorder, it is common to find a low ceruloplasmin level, an elevated serum free copper level, and an elevated urinary copper level. Liver biopsy reveals an elevated hepatic copper concentration in the range of 250-3,000 micrograms/gram dry weight. Hypoceruloplasminemia is not specific to Wilsons disease and is observed with liver failure of any etiology. A normal ceruloplasmin level may be present in Wilsons disease, or the ceruloplasmin may be falsely elevated as ceruloplasmin is an acute phase reactant and is elevated secondary to inflammation. All persons with untreated Wilsons disease will have an elevated hepatic copper content. However, not all persons with an elevated hepatic copper content have Wilsons disease as this abnormality is also seen with cholestatic disorders.

Common associated lab abnormalities include the above mentioned Coombs-negative intravascular hemolysis plus a strikingly low serum alkaline phosphatase level, modest transaminasemia (AST is characteristically greater than ALT) and hyperbilirubinemia. The alkaline phosphatase to total bilirubin ratio is usually less than two.

Diagnosis is established by the presence of Kayser-Fleischer rings plus hypoceruloplasminemia (<20 mg/dL). If Kayser-Fleischer rings are absent, hypoceruloplasminemia plus an elevated hepatic copper concentration establishes the diagnosis. If Wilsons disease is suspected but the above-mentioned abnormalities are absent, a radiocopper incorporation study can be performed.

Treatment includes copper chelation therapy using penicillamine (500 mg PO QID) or triethylene tetramine dihydrochloride (500 mg PO TID). Both should be administered on an empty stomach. Persons on penicillamine should be observed for signs of myasthenia gravis, as this is a potential side effect. Zinc sulfate or zinc acetate (150 mg PO TID) competitively inhibits intestinal copper absorption, and is an effective treatment alternative. In cases with severe hepatic damage, liver transplantation is necessary. Liver transplantation is curative and corrects the underlying metabolic defect.