• Albert Friedrich Stättermayer, Andreas Entenmann, Michael Gschwantler, Heinz Zoller, Harald Hofer, and Peter Ferenci.
• Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
• Eur. J. Clin. Invest. 2019 Aug 1; 49 (8): e13147.

BackgroundWilson disease (WD) is an autosomal recessive disorder of hepatic copper excretion. About sixty per cent of patients present with liver disease. WD is considered a fatal disease if undiagnosed and/or untreated but recent data indicate that disease penetrance may not be 100%.Materials And MethodsAll patients underwent liver biopsy as part of the diagnostic workup. Genetic testing for ATP7B was performed by Sanger sequencing.ResultsWe report on a large family with multiple affected siblings. The first patient (male, 31 years) underwent orthotopic liver transplantation (OLT) because of fulminant WD. He was homozygous for p.G710A. One asymptomatic brother (37 years) had the same mutation. He is doing well on chelation therapy. Fifteen years later, a second-degree sibling (female, 16 years) presented with fulminant WD and underwent OLT. She was compound heterozygote (p.G710A/p.G710S). Further family screening revealed a third mutation (p.V536A) in a female (21 years) and male (16 years) compound-heterozygote sibling (p.G710A/p.V536A). In both, serum ceruloplasmin and 24-hour urinary copper excretion were normal. Liver biopsy showed normal histology and a quantitative hepatic copper content within the normal range or only slightly elevated (19 and 75 μg/g dry weight, respectively). No decoppering treatment was initiated so far.ConclusionGenetic testing alone is not always sufficient to diagnose WD in asymptomatic patients, and human mutation databases should be used with caution. Even patients carrying two disease-causing mutations do not necessarily have demonstrable alteration of copper metabolism. Asymptomatic siblings diagnosed by genetic screening require further testing before initiating treatment.© 2019 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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