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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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.
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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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