Clinical molecular diagnosis of Wilson disease

Wilson disease is an autosomal recessive disorder of copper transport characterized by toxic accumulation of copper in the liver, brain, and other organs. It is lethal if untreated, but effective treatment is available. The broad spectrum of clinical manifestations, including hepatic and neuropsychiatric symptoms, can present over a large age range, contributing to difficulty in recognition of this disease. The diagnosis has traditionally rested on measurements of ceruloplasmin and copper in urine and liver, but it remains a challenge due to ambiguous biochemical results that can overlap with healthy carriers. Although hepatic copper concentration has been the gold standard for diagnosis, direct sequencing of the ATP7B gene is sensitive, specific, and can obviate the need for invasive liver biopsy. In this article, the authors review the sensitivity, limitations, and pitfalls of ATP7B sequencing in the diagnosis of Wilson disease. ATP7B sequencing should be standard practice in the diagnosis of Wilson disease.