Wilson disease (WD) is a disorder of hepatic copper disposition caused by mutations in the gene ATP7B, on chromosome 13, which encodes a metal-transporting P1-type ATPase, known as the Wilson ATPase. In hepatocytes the Wilson ATPase assists in moving copper across intracellular membranes, which directly contributes to production of ceruloplasmin, a ferroxidase that is functional only when copper is incorporated. Additionally, the Wilson ATPase expedites excretion of copper into bile. Accordingly, in WD serum concentrations of ceruloplasmin are low and hepatic retention of copper develops, leading to liver injury. With progression of liver disease, copper spills out of the liver and accumulates in other organs, such as the brain, eyes, renal tubules, heart, and synovial membranes. Untreated WD is a progressive degenerative disease, nearly always associated with early death.
WD occurs worldwide, but it is rare. The average prevalence is 30 affected persons per million population, with a corresponding carrier frequency of approximately 1 in 90. More than 500 mutations have been identified, and 80% of affected individuals are compound heterozygotes. In some populations (including Iceland, Korea, Japan, Sardinia, and the Canary Islands) where the incidence in higher, there may also be a relatively circumscribed set of mutations. In northeastern Europe, the mutation H1069Q is found as at least one of the mutations in 35% to 75% of WD patients.