{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T15:27:09Z","timestamp":1780932429012,"version":"3.54.1"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Wilson 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%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>All patients underwent liver biopsy as part of the diagnostic workup. Genetic testing for ATP7B was performed by Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report on a large family with multiple affected siblings. The first patient (male, 31\u00a0years) underwent orthotopic liver transplantation (OLT) because of fulminant WD. He was homozygous for p.G710A. One asymptomatic brother (37\u00a0years) had the same mutation. He is doing well on chelation therapy. Fifteen years later, a second\u2010degree sibling (female, 16\u00a0years) 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\u00a0years) and male (16\u00a0years) compound\u2010heterozygote sibling (p.G710A\/p.V536A). In both, serum ceruloplasmin and 24\u2010hour 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\u00a0\u03bcg\/g dry weight, respectively). No decoppering treatment was initiated so far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Genetic 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\u2010causing mutations do not necessarily have demonstrable alteration of copper metabolism. Asymptomatic siblings diagnosed by genetic screening require further testing before initiating treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13147","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T09:15:11Z","timestamp":1559812511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["The dilemma to diagnose Wilson disease by genetic testing alone"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0737-4091","authenticated-orcid":false,"given":"Albert Friedrich","family":"St\u00e4ttermayer","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Entenmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Innsbruck Medical University Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gschwantler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV Wilhelminenspital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Zoller","sequence":"additional","affiliation":[{"name":"Department of Medicine I, Gastroenterology, Hepatology and Endocrinology Innsbruck Medical University Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Hofer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III Medical University of Vienna Vienna Austria"},{"name":"Department of Internal Medicine I Klinikum Wels\u2010Grieskirchen Wels Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Ferenci","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine III Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.11.007"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0018-3"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50281"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00232-002-1040-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-115-9-720"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0676.2003.00824.x"},{"key":"e_1_2_7_8_1","first-page":"744","article-title":"Wilson\u2019s disease in the German Democratic Republic. 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