{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:05:14Z","timestamp":1784624714874,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Wilson disease (WD) diagnosis remains challenging due to variable biomarker performance across clinical presentations. Exchangeable copper (CuEXC) directly quantifies non\u2010ceruloplasmin\u2010bound copper (NCC), the pathogenic copper fraction. We assessed the diagnostic accuracy of CuEXC across WD phenotypes and its utility for evaluating disease severity. In this prospective study (NCT05231876) at the French National Reference Center for WD, we enrolled 158 treatment\u2010na\u00efve patients (48% female; mean age 20\u2009\u00b1\u200914\u2009years; 44% \u2264\u200918\u2009years) referred between 2009 and 2025. Clinical presentations included asymptomatic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200911), hepatic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200987), and neurologic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200960). CuEXC was measured at diagnosis and compared against ceruloplasmin, total copper, relative exchangeable copper (REC), and 24\u2010h urinary copper using ROC analysis. Seven patients with hemolytic anemia uniformly associated with acute liver failure had extreme CuEXC elevations (median 11.0\u2009\u03bcmol\/L) and were excluded from ROC analyses. CuEXC increased stepwise across phenotypes (0.8, 1.6, and 2.9\u2009\u03bcmol\/L;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). CuEXC distinguished advanced from mild\u2010to\u2010moderate liver disease (AUC 0.86; 95% CI, 0.82\u20130.89; optimal threshold 1.8\u2009\u03bcmol\/L: sensitivity 83%, specificity 87%) and differentiated neurologic from hepatic presentations (AUC 0.87; 95% CI, 0.80\u20130.93; optimal threshold 2.07\u2009\u03bcmol\/L: sensitivity 88%, specificity 81%; pragmatic cutoff 2.0\u2009\u03bcmol\/L: sensitivity 91%, specificity 80%). Performance was consistent across age groups. CuEXC outperformed other biomarkers in head\u2010to\u2010head comparisons. After excluding hemolysis, CuEXC\u2009\u2265\u20091.8\u2009\u03bcmol\/L supports screening for advanced liver disease, even without clinical or laboratory liver abnormalities. CuEXC\u2009\u2265\u20092.0\u2009\u03bcmol\/L warrants expedited neurologic assessment and may help distinguish neuro Wilson from hepatic encephalopathy. CuEXC enhances early risk stratification for timely intervention in WD.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70178","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:02:29Z","timestamp":1775721749000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Accuracy of Exchangeable Copper for Grading the Severity of Wilson Disease"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-9590","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Desjardins","sequence":"first","affiliation":[{"name":"National Reference Center for Wilson's Disease and Other Copper\u2010Related Rare Diseases Rothschild Foundation Hospital  Paris France"},{"name":"Department of Neurology Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouzha","family":"Oussedik\u2010Djebrani","sequence":"additional","affiliation":[{"name":"National Reference Center for Wilson's Disease and Other Copper\u2010Related Rare Diseases Rothschild Foundation Hospital  Paris France"},{"name":"Toxicology Department, Lariboisiere Hospital AP\u2010HP and INSERM OTEN U1144 Paris\u2010Cit\u00e9 University  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mickael Alexandre","family":"Obadia","sequence":"additional","affiliation":[{"name":"National Reference Center for Wilson's Disease and Other Copper\u2010Related Rare Diseases Rothschild Foundation Hospital  Paris France"},{"name":"Department of Neurology Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djamila","family":"Rahli","sequence":"additional","affiliation":[{"name":"National Reference Center for Wilson's Disease and Other Copper\u2010Related Rare Diseases Rothschild Foundation Hospital  Paris France"},{"name":"Department of Clinical Research Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Le Cossec","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"France","family":"Woimant","sequence":"additional","affiliation":[{"name":"National Reference Center for Wilson's Disease and Other Copper\u2010Related Rare Diseases Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Debray","sequence":"additional","affiliation":[{"name":"National Reference Center for Wilson's Disease and Other Copper\u2010Related Rare Diseases Rothschild Foundation Hospital  Paris France"},{"name":"Department of Neurology Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5640-7534","authenticated-orcid":false,"given":"Aur\u00e9lia","family":"Poujois","sequence":"additional","affiliation":[{"name":"National Reference Center for Wilson's Disease and Other Copper\u2010Related Rare Diseases Rothschild Foundation Hospital  Paris France"},{"name":"Department of Neurology Rothschild Foundation Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2018.03.007"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010018\u20100018\u20103"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2025.101537"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.11.007"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22261"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001787"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169316"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12348"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.02.48"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2025.100939"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12418"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfae058"},{"key":"e_1_2_12_14_1","first-page":"43","volume-title":"Handbook of Clinical Neurology","author":"Scheiber I. 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