[Pathogenesis of Wilson's disease]

Wilson disease is due to a genetically determined impairment of copper excretion from liver into bile resulting in copper overload of the organism. The chromosomal defect and the primary defect of copper metabolism is not yet defined. When during the course of the disease the cytoplasmatic copper binding sites of hepatocytes are saturated, excess of "free" copper is accumulating. It induces liver cell damage and necrosis followed by the development of fibrosis and cirrhosis. The accumulation process of excess free copper in hepatocytes is accompanied by a redistribution into the lysosomal compartment of the cells as well as by release of free copper into blood. This increase of the free serum copper concentration leads during the course of the disease to an elevated copper burden of other organs. This results in a variety of symptoms, of which liver disease and neurologic disturbances are of major significance in regard to clinical presentation and prognosis of the patients.