Diagnosis and Treatment of Wilson Disease

AASLD develops evidence-based practice guidelines and practice guidances which are updated regularly by a committee of hepatology experts and include recommendations of preferred approaches to the diagnostic, therapeutic, and preventive aspects of care. 

Practice Guideline

Diagnosis and Treatment of Wilson Disease: An Update [updated June 2008]

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. 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. In 1993, the abnormal gene in WD was identified. 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 ceruloplasmin protein without copper, apoceruloplasmin, result in the decreased blood level of ceruloplasmin found in most patients with WD due to the reduced half-life of apoceruloplasmin.