Therapy of Wilson disease

Wilson disease is a copper storage disease with autosomal-recessive trait that is predominantly a disorder of the adolescent and young adult. Clinical manifestations are dominated by hepatic and/or neurological symptoms. Diagnostic procedures include determination of total serum cop per: free serum copper and serum ceruloplamin concentrations as well as urinary copper excretion. Confirmation of diagnosis may be achieved by liver biopsy and histological determination of copper content. The aim of treatment is reduction of tissue copper concentration and detoxification of copper. Drugs applied are the chelating agents. D-penicillamine and trientine, or zinc. The chelating agents induce renal and biliary copper excretion and increased synthesis of metallothionein, which attaches and detoxifies intracellular copper, leading to impaired absorption and binding of excess intracellular copper. Treatment with zinc results in induction of hepatic and intestinal metallothionein synthesis. Regular examinations of the parameters of copper metabolism are necessary in order to control the therapeutic effect. Free copper serum concentrations and urinary copper excretion should reach values below 10 mu g/dl and 80 mu g/day. respectively. A significant improvement of clinical symptoms and normalization of parameters of copper metabolism can be expected earliest six months after onset of therapy. Anti-copper treatment ma!: be accompanied by copper-reduced diet. Lifelong therapy is required and provides life-expectancy near to normal. Interruption of treatment leads to reaccumulation of copper, often resulting in fulminant hepatic failure. This can also be observed as initial presentation in 5% of cases (predominant age 12 to;25 years). End stage liver disease and fulminant hepatic failure are indications for liver transplantation by which the genetic defect is phenotypically cured. Here decoppering treatment is no longer required. whether severe neurological disorders may also be improved is not clear until today.