Wilson disease is an inherited abnormality of copper metabolism that leads to excess copper accumulation and injury to liver, brain and other organs. The metabolic defect in Wilson disease is caused by mutations in ATPase7B, a hepatic enzyme responsible for transmembrane transport and excretion of copper into the bile. The metabolic defect leads to accumulation of free copper in liver and blood and secondarily in other organs, particularly brain and kidney. The disease usually presents in childhood or adolescence with neurologic syndromes, signs of advanced liver disease and hemolytic anemia. If untreated it is invariably fatal, death being from progressive neurologic disease or acute or chronic liver failure. Therapy of Wilson disease is usually based upon copper chelation, but limitation of copper in the diet and approaches to inhibiting copper absorption can also be important.
Copper chelating agents available in the United States include penicillamine, trientine and dimercaprol. These agents lower blood and tissue copper levels and, when given chronically, prevent copper accumulation and injury in Wilson disease. Penicillamine is considered the first line therapy of Wilson disease, but is often limited by its unique side effects that can be severe and may be dose limiting. Trientine is a second line agent and is less effective than penicillamine in chelating copper, but it has fewer serious side effects and is generally well tolerated. Both of these agents are given orally. Dimercaprol (also known as British anti-Lewisite or BAL) was the initial copper chelating agent developed for Wilson disease, but it requires parenteral administration and has frequent serious adverse effects. Dimercaprol is currently rarely used for Wilson disease and generally only in conjunction with oral copper chelating agents, for a short period of time, and in patients with severe symptomatic disease. Zinc is also useful in managing Wilson disease and acts by inhibition of copper absorption, rather than chelation of excess copper in tissue or the circulation. Zinc has been used as a first line therapy, but is currently recommended largely as maintenance therapy once chelation of excess copper has been accomplished.
Among the drugs used for Wilson disease, only penicillamine has been linked to cases of clinically apparent liver injury. Penicillamine has been linked to cases of acute, immunoallergic hepatitis which is likely due to hypersensitivity.