Wilson's disease. Update of a systemic disorder with protean manifestations

Abstract

In Wilson's disease, a genetic defect in a copper transporter causes defective incorporation of copper into apo-ceruloplasmin and the failure to excrete copper into bile. Copper accumulated in hepatocytes generates damage via reactive oxygen species. Release of copper from necrotic hepatocytes leads to damage of other tissues, including the brain, urinary tract, red blood cells, heart, endocrine glands, skin, pancreas, bones, and joints. Treatment is designed to chelate the excess copper for urinary excretion, prevent copper absorption, and render tissue copper nontoxic. Liver transplantation, with replacement of the defective hepatic gene, may be necessary in some cases.