Wilson disease is an autosomal recessive inherited disorder of
copper metabolism resulting in pathological accumulation of
copper in many organs and tissues. ATP7B is the gene product of the
Wilson disease gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting
copper into the secretory pathway for incorporation into
apoceruloplasmin and excretion into the bile. Mutations of the gene result in impaired trafficking of
copper in and through the hepatocytes. More than 200 mutations of
Wilson disease gene were found, the most common ones being H1069Q (in Europe) and R778L (in Asia).
Wilson disease may present under a variety of clinical conditions, commonly as liver and/or neuropsychiatric disease. The pathogenesis of hepatic and neurologic
Wilson disease is a direct consequence of
copper accumulation. Presence of
copper causes oxidative stress resulting in cell destruction. The diagnosis of
Wilson disease requires a combination of a variety of clinical symptoms, biochemical tests, and detection of gene mutations, which are the basis of a score proposed by a group of international experts. Initial treatment for symptomatic patients should include a
chelating agent (
penicillamine or
trientine). Treatment of presymptomatic patients or maintenance
therapy can also be accomplished with
zinc.