{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:11:32Z","timestamp":1760130692542,"version":"build-2065373602"},"reference-count":20,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T00:00:00Z","timestamp":1692662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Crigler\u2013Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler\u2013Najjar Syndrome. Most of these patients need medical treatment for enzyme induction (phenobarbital) to lower blood levels of unconjugated bilirubin (UCB). Apart from this, no long-term problems have been described so far. The phenotype of patients with the homozygous pathogenic variant c.115C&gt;G p.(His39Asp) in UGT1A1 is described as variable. Clinical observations of our patients led to the assumption that patients with variant c.115C&gt;G have a mild CNS phenotype while having a high risk of developing progressive liver disease. For mild CNS disease, progressive liver disease has not been described so far. Therefore, we conducted a retrospective multicenter analysis of 14 patients with this particular variant, aiming for better characterization of this variant. We could confirm that patients with variant c.115C&gt;G have a high risk of progressive liver disease (seven of fourteen), which increases with age despite having a very mild CNS phenotype. Earlier predictors and causes for an unfavorable disease course are not detectable, but close follow-up could identify patients with progressive liver disease at the beginning. In conclusion, these patients need close and specialized follow-up. Our study questions whether fibrosis in the CNS is really driven by high amounts of UCB or phototherapy.<\/jats:p>","DOI":"10.3390\/children10091431","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T09:10:56Z","timestamp":1692695456000},"page":"1431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mild Crigler\u2013Najjar Syndrome with Progressive Liver Disease\u2014A Multicenter Retrospective Cohort Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-2667","authenticated-orcid":false,"given":"Norman","family":"Junge","sequence":"first","affiliation":[{"name":"Department of Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30626 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Hentschel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothee","family":"Krebs-Schmitt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amelie","family":"Stalke","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30626 Hannover, Germany"},{"name":"Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva-Doreen","family":"Pfister","sequence":"additional","affiliation":[{"name":"Department of Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30626 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Hartleben","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Hannover Medical School, 30626 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Cla\u00dfen","sequence":"additional","affiliation":[{"name":"Prof.-Hess-Childrens Hospital, Klinikum Bremen Mitte, Gesundheit Nord GmbH, 28205 Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Querfurt","sequence":"additional","affiliation":[{"name":"Prof.-Hess-Childrens Hospital, Klinikum Bremen Mitte, Gesundheit Nord GmbH, 28205 Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronika","family":"M\u00fcnch","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5742-8273","authenticated-orcid":false,"given":"Philip","family":"Bufler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charit\u00e9 Universit\u00e4tsmedizin Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-675X","authenticated-orcid":false,"given":"Jun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enke","family":"Grabhorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.2174\/1871530318666171213153130","article-title":"Crigler-Najjar Syndrome: Current Perspectives and the Application of Clinical Genetics","volume":"18","author":"Ebrahimi","year":"2018","journal-title":"Endocr. 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