{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:59:36Z","timestamp":1792025976709,"version":"4.4.0"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Wilson's disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000\u00a0live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24\u2010hour urinary copper, and ceruloplasmin using the Leipzig criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adhering to PRISMA guidelines, databases including PubMed\/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nine studies were included. The best practice evidence for 24\u2010hour urinary copper test ranged from a cutoff value of 0.64\u20131.6\u00a0\u03bcmol\/24\u00a0h (<jats:italic>N<\/jats:italic>\u00a0=\u00a0268; sensitivity\u00a0=\u00a075.6%, specificity\u00a0=\u00a098.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2\u00a0\u03bcmol\/g yielding a power of 96.4% sensitivity and 95.4% specificity (<jats:italic>N<\/jats:italic>\u00a0=\u00a01,150); however, the tried and tested 4\u00a0\u03bcmol\/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2\u00a0g\/L (<jats:italic>N<\/jats:italic>\u00a0=\u00a04,281; sensitivity\u00a0=\u00a077.1%\u201399%, specificity\u00a0=\u00a055.9%\u201382.8%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This paper provides a large\u2010scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over\u2010 or under\u2010estimation of the index tests.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24191","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T07:46:32Z","timestamp":1640331992000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Biochemical testing for the diagnosis of Wilson's disease: A systematic review"],"prefix":"10.1002","volume":"36","author":[{"given":"Hafiz Muhammad","family":"Salman","sequence":"first","affiliation":[{"name":"Services Institute of Medical Sciences Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahwish","family":"Amin","sequence":"additional","affiliation":[{"name":"Sir Ganga Ram Hospital Lahore, Punjab Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javaria","family":"Syed","sequence":"additional","affiliation":[{"name":"Sargodha Medical College Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-7455","authenticated-orcid":false,"given":"Zouina","family":"Sarfraz","sequence":"additional","affiliation":[{"name":"Fatima Jinnah Medical University Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8206-5745","authenticated-orcid":false,"given":"Azza","family":"Sarfraz","sequence":"additional","affiliation":[{"name":"The Aga Khan University Karachi Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzna","family":"Sarfraz","sequence":"additional","affiliation":[{"name":"King Edward Medical University Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Jose","family":"Farf\u00e1n Baja\u00f1a","sequence":"additional","affiliation":[{"name":"Universidad Esp\u00edritu Santo Samborond\u00f3n Ecuador"},{"name":"Respiralab, Respiralab Research Group Guayaquil Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Felix","sequence":"additional","affiliation":[{"name":"Universidad Esp\u00edritu Santo Samborond\u00f3n Ecuador"},{"name":"Respiralab, Respiralab Research Group Guayaquil Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Cherrez\u2010Ojeda","sequence":"additional","affiliation":[{"name":"Universidad Esp\u00edritu Santo Samborond\u00f3n Ecuador"},{"name":"Respiralab, Respiralab Research Group Guayaquil Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70190-5"},{"issue":"11","key":"e_1_2_8_3_1","first-page":"CD012267","article-title":"Biomarkers for diagnosis of Wilson\u2019s disease","volume":"2019","author":"Ryan A","year":"2019","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2010.07.014"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1010539520927259"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.132"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.02.016"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463200501800102"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408360801991055"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v13.i6.634"},{"key":"e_1_2_8_11_1","first-page":"n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"2021","author":"Page MJ","year":"2020","journal-title":"BMJ"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23910"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.5152\/tjg.2014.7787"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190887"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.06.022"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.103432"},{"issue":"1","key":"e_1_2_8_17_1","first-page":"49","article-title":"The reassessment of the diagnostic value of 24\u2010hour urinary copper excretion in children with Wilson\u2019s disease. 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