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Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study
Crigler–Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler–Najjar Syndrome. Most of these patients need medical treatment for enzyme induction (phenobarbital) to lower blood levels of unconjugated bilirub...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527646/ https://www.ncbi.nlm.nih.gov/pubmed/37761392 http://dx.doi.org/10.3390/children10091431 |
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author | Junge, Norman Hentschel, Hanna Krebs-Schmitt, Dorothee Stalke, Amelie Pfister, Eva-Doreen Hartleben, Björn Claßen, Martin Querfurt, Alexander Münch, Veronika Bufler, Philip Oh, Jun Grabhorn, Enke |
author_facet | Junge, Norman Hentschel, Hanna Krebs-Schmitt, Dorothee Stalke, Amelie Pfister, Eva-Doreen Hartleben, Björn Claßen, Martin Querfurt, Alexander Münch, Veronika Bufler, Philip Oh, Jun Grabhorn, Enke |
author_sort | Junge, Norman |
collection | PubMed |
description | Crigler–Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler–Najjar 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>G p.(His39Asp) in UGT1A1 is described as variable. Clinical observations of our patients led to the assumption that patients with variant c.115C>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>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. |
format | Online Article Text |
id | pubmed-10527646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105276462023-09-28 Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study Junge, Norman Hentschel, Hanna Krebs-Schmitt, Dorothee Stalke, Amelie Pfister, Eva-Doreen Hartleben, Björn Claßen, Martin Querfurt, Alexander Münch, Veronika Bufler, Philip Oh, Jun Grabhorn, Enke Children (Basel) Article Crigler–Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (UGT1A1) and no need for daily phototherapy is called mild Crigler–Najjar 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>G p.(His39Asp) in UGT1A1 is described as variable. Clinical observations of our patients led to the assumption that patients with variant c.115C>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>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. MDPI 2023-08-22 /pmc/articles/PMC10527646/ /pubmed/37761392 http://dx.doi.org/10.3390/children10091431 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Junge, Norman Hentschel, Hanna Krebs-Schmitt, Dorothee Stalke, Amelie Pfister, Eva-Doreen Hartleben, Björn Claßen, Martin Querfurt, Alexander Münch, Veronika Bufler, Philip Oh, Jun Grabhorn, Enke Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study |
title | Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study |
title_full | Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study |
title_fullStr | Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study |
title_full_unstemmed | Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study |
title_short | Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study |
title_sort | mild crigler–najjar syndrome with progressive liver disease—a multicenter retrospective cohort study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10527646/ https://www.ncbi.nlm.nih.gov/pubmed/37761392 http://dx.doi.org/10.3390/children10091431 |
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