{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T09:14:33Z","timestamp":1789204473122,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Paediatrics Child Health"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neonatal cholestasis is a group of disorders characterised by conjugated hyperbilirubinemia in the newborns and young infants. Advances in genetic testing have facilitated the identification of specific aetiology. This study examines the genetic and clinical profiles of neonates with cholestasis, focusing on genotype\u2013phenotype correlations and diagnostic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective review of children with neonatal cholestasis treated between 1997 and 2024 was conducted. Extrahepatic causes were excluded, and genetic testing, including a targeted cholestasis panel and whole exome sequencing (WES), was employed. Clinical and biochemical data, including gamma\u2010glutamyl transferase (GGT) levels, were collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetic disorders were identified in 28.0% of 378 cases, including mutations in ATP8B1, ABCB11, ABCB4, DCDC2, DGUOK, KIF12, USP53, and genes related to bile acid synthesis (HSD3B7, PEX1). GGT levels played a significant role in diagnosis: patients with low or normal GGT were frequently diagnosed with progressive familial intrahepatic cholestasis (PFIC)1 and 2, or bile acid synthesis defects, while high GGT levels were associated with PFIC3, alpha\u20101 antitrypsin deficiency, and cystic fibrosis. Consanguinity was noted in 56.0% of genetically diagnosed cases. After 2010, 35.5% of patients received a genetic diagnosis, compared to 18.2% before 2010.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Genetic diseases are a major cause of neonatal cholestasis, and GGT levels serve as a useful diagnostic tool in differentiating subtypes. The increasing availability of genetic testing has improved early diagnosis and personalised management. Expanded genetic testing in clinical practice is critical for timely and accurate diagnosis of these rare disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jpc.70072","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T02:20:07Z","timestamp":1745979607000},"page":"1049-1055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Neonatal Cholestasis: Exploring Genetic Causes and Clinical Outcomes"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1813-7780","authenticated-orcid":false,"given":"Neslihan","family":"G\u00fcrcan Kaya","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology Ankara Training and Research Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-6019","authenticated-orcid":false,"given":"Hakan","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Gazi\u00a0University Faculty of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6316-4593","authenticated-orcid":false,"given":"Sinan","family":"Sar\u0131","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Gazi\u00a0University Faculty of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-7551","authenticated-orcid":false,"given":"\u00d6d\u00fcl","family":"E\u011frita\u015f G\u00fcrkan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Gazi\u00a0University Faculty of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4678-8764","authenticated-orcid":false,"given":"Buket","family":"Dalg\u0131\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology Gazi\u00a0University Faculty of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001334"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/neo.14\u20102\u2010e63"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.804"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2005.10.008"},{"key":"e_1_2_8_6_1","first-page":"52","article-title":"Genetic Profiling of Children With Advanced Cholestatic Liver Disease","volume":"92","author":"Shagrani M.","year":"2017","journal-title":"Journal of Clinical Gastroenterology"},{"key":"e_1_2_8_7_1","first-page":"1837","article-title":"The Genetics of Inherited Cholestatic Disorders in Neonates and Infants: Evolving Challenges","volume":"12","author":"Jeyaraj R.","year":"2021","journal-title":"Genetics in Medicine"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sempedsurg.2020.150945"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.01.006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-019-0548-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2019.04.016"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.09.028"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2023.1094895"},{"key":"e_1_2_8_14_1","first-page":"115","article-title":"Two Cases With Neonatal Cholestasis and Renal Disorders due to DCDC2 Mutation","volume":"20","author":"D\u00fczta\u015f D. 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S.","year":"2008","journal-title":"Journal of Neonatal Hepatology"},{"key":"e_1_2_8_18_1","first-page":"1","article-title":"Genetic Spectrum and Clinical Characteristics of 3\u03b2\u2010Hydroxy\u2010\u03945\u2010C27\u2010Steroid Oxidoreductase (HSD3B7) Deficiency in China","volume":"16","author":"Zhao J.","year":"2021","journal-title":"Journal of Hepatology"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200206000-00008"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1542\/neo.22\u201012\u2010e819"}],"container-title":["Journal of Paediatrics and Child Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpc.70072","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T08:56:42Z","timestamp":1751360202000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpc.70072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/jpc.70072"],"URL":"https:\/\/doi.org\/10.1111\/jpc.70072","archive":["Portico"],"relation":{},"ISSN":["1034-4810","1440-1754"],"issn-type":[{"value":"1034-4810","type":"print"},{"value":"1440-1754","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,29]]},"assertion":[{"value":"2025-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}