Clinical meaning
Wilson disease (hepatolenticular degeneration) is an autosomal recessive disorder of copper metabolism caused by mutations in the ATP7B gene on chromosome 13, encoding a copper-transporting P-type ATPase expressed primarily in hepatocytes. ATP7B serves two critical functions: (1) incorporating copper into apoceruloplasmin to form ceruloplasmin (the major copper-carrying protein in plasma), and (2) excreting excess copper into bile (the primary route of copper elimination from the body). When ATP7B is dysfunctional, both processes fail: ceruloplasmin levels fall (typically <20 mg/dL) because copper cannot be loaded into the protein, and biliary copper excretion ceases, causing progressive copper accumulation first in the liver, then in the brain (particularly the basal ganglia, putamen, and caudate nucleus), cornea (Descemet membrane), kidneys, and other organs. Hepatic copper accumulation causes a spectrum of liver disease from asymptomatic transaminase elevation through chronic active hepatitis to macronodular cirrhosis to fulminant hepatic failure. Fulminant Wilson disease presents with acute liver failure, Coombs-negative hemolytic anemia (copper released from necrotic hepatocytes oxidizes RBC membranes causing intravascular hemolysis), acute kidney injury, and markedly elevated serum copper. Neurological manifestations result from copper deposition in...