The Diagnostic Approach to Wilson Disease

Abstract The diagnosis of Wilson disease (WD) should be excluded in any patient with unexplained deranged liver function tests with or without neurological or psychiatric disease. WD is a rare inherited disorder of copper metabolism due to a mutation of the ATP7B gene. The clinical presentations can vary widely; the symptoms are often nonspecific and can affect different organ systems due to the accumulation of toxic copper. WD can be present at any age, not just in children and young adults. No single investigation is diagnostic, and often, a combination of tests is required to confirm the diagnosis. None of the available laboratory investigations are ideal and specific. A detailed physical examination including neurological, eye, and abdominal examination is essential. To secure the diagnosis, a number of parameters are scored 0 (absent) to 2 (present), including laboratory features (copper in the serum, liver, and urine; serum ceruloplasmin; and genetic testing) and clinical signs (including Kayser-Fleischer Rings), each used for the calculation of the Leipzig score. If the score is > 4, the diagnosis of WD is very likely. Screening of relatives with mutation analysis in those with confirmed WD is imperative to detect patients at an early stage where disease progression can be prevented with medical therapy. Occasionally, WD patients present with acute liver failure (ALF), in which case ALF itself may alter copper parameters and complicate the diagnosis further. Serological ratios have been proposed to support the diagnosis in this situation. Diagnosing WD in ALF is essential as liver transplant is curative and lifesaving.