Copper is an essential metal that is an important cofactor for many proteins. The average diet provides substantial amounts of copper, typically 2-5 mg/day; the recommended intake is 0.9 mg/day. Most dietary copper ends up being excreted. Copper is absorbed by enterocytes mainly in the duodenum and proximal small intestine and transported in the portal circulation in association with albumin and the amino acid histidine to the liver, where it is avidly removed from the circulation. The liver utilizes some copper for metabolic needs, synthesizes and secretes the copper-containing protein ceruloplasmin, and excretes excess copper into bile. Processes that impair biliary copper excretion can lead to increases in hepatic copper content.

Wilson disease (WD; also known as hepatolenticular degeneration) was first described in 1912 by Kinnear Wilson as “progressive lenticular degeneration,” a familial, lethal neurological disease accompanied by chronic liver disease leading to cirrhosis. 5 Over the next several decades, the role of copper in the pathogenesis of WD was established, and the pattern of inheritance was determined to be autosomal recessive. 6, 7 In 1993, the abnormal gene in WD was identified. 8-10 This gene, ATP7B, encodes a metal-transporting P-type adenosine triphosphatase (ATPase), which is expressed mainly in hepatocytes and functions in the transmembrane transport of copper within hepatocytes. Absent or reduced function of ATP7B protein leads to decreased hepatocellular excretion of copper into bile. This results in hepatic copper accumulation and injury. Eventually, copper is released into the bloodstream and deposited in other organs, notably the brain, kidneys, and cornea. Failure to incorporate copper into ceruloplasmin is an additional consequence of the loss of functional ATP7B protein. The hepatic production and secretion of the ceruloplas-