Wilson Disease

Causes/Genetics/History

Wilson disease is a genetic disorder that is thought to affect one in 50,000 to 100,000 people worldwide. The disorder is due to abnormal changes (mutations) in a gene that is inherited as an autosomal recessive trait. The disease gene responsible for Wilson disease, known as the ATP7B gene, is located on the long arm (q) of chromosome 13 (13q14.3). The protein regulated by this gene plays a role in the transport of copper (copper-transporting ATPase).

Recessively transmitted disorders may be fully expressed in individuals who inherit two copies of the disease gene (homozygotes), one from the mother and one from the father. Brothers or sisters of those diagnosed with Wilson disease have a one in four chance of inheriting two copies of the disease gene and thus developing the disease. Those who inherit a single copy of the disease gene (heterozygotes) are carriers of the disease trait and may transmit a single copy of the disease gene to their children. It is estimated that one in 90 to 100 individuals is a carrier for Wilson disease. Genetic testing for Wilson disease is not yet possible. However, in families with known, mutations of the gene, haplotype analysis may be useful in determining carrier status.

The basic underlying defect in Wilson disease is not known. It may be related to the body's inability to produce sufficient levels of ceruloplasmin, an enzyme in the fluid portion of the blood that binds to copper and is involved in its transport and regulation. Other scientists theorize that reduced production of ceruloplasmin may be the result of a defect in the liver's ability to metabolize or break down copper. The relationship between reduced ceruloplasmin levels and excessive copper accumulation is not understood. In addition, there is some evidence of impaired excretion of copper by the biliary system.