Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study
Crigler–Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (<i>UGT1A1</i>) 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 u...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Children |
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| Online Access: | https://www.mdpi.com/2227-9067/10/9/1431 |
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| author | Norman Junge Hanna Hentschel Dorothee Krebs-Schmitt Amelie Stalke Eva-Doreen Pfister Björn Hartleben Martin Claßen Alexander Querfurt Veronika Münch Philip Bufler Jun Oh Enke Grabhorn |
| author_facet | Norman Junge Hanna Hentschel Dorothee Krebs-Schmitt Amelie Stalke Eva-Doreen Pfister Björn Hartleben Martin Claßen Alexander Querfurt Veronika Münch Philip Bufler Jun Oh Enke Grabhorn |
| author_sort | Norman Junge |
| collection | DOAJ |
| description | Crigler–Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (<i>UGT1A1</i>) 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. |
| first_indexed | 2024-03-10T22:54:49Z |
| format | Article |
| id | doaj.art-020f058aa8284c33b0d8290f19ed74fa |
| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-10T22:54:49Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj.art-020f058aa8284c33b0d8290f19ed74fa2023-11-19T10:02:24ZengMDPI AGChildren2227-90672023-08-01109143110.3390/children10091431Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort StudyNorman Junge0Hanna Hentschel1Dorothee Krebs-Schmitt2Amelie Stalke3Eva-Doreen Pfister4Björn Hartleben5Martin Claßen6Alexander Querfurt7Veronika Münch8Philip Bufler9Jun Oh10Enke Grabhorn11Department of Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30626 Hannover, GermanyDepartment of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30626 Hannover, GermanyDepartment of Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, 30626 Hannover, GermanyInstitute of Pathology, Hannover Medical School, 30626 Hannover, GermanyProf.-Hess-Childrens Hospital, Klinikum Bremen Mitte, Gesundheit Nord GmbH, 28205 Bremen, GermanyProf.-Hess-Childrens Hospital, Klinikum Bremen Mitte, Gesundheit Nord GmbH, 28205 Bremen, GermanyDepartment of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Pediatric Gastroenterology, Nephrology and Metabolic Diseases, Charité Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyDepartment of Pediatrics, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, GermanyCrigler–Najjar Syndrome (CNS) with residual activity of UDP-glucuronosyltransferase 1A1 (<i>UGT1A1</i>) 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.https://www.mdpi.com/2227-9067/10/9/1431liver fibrosisliver transplantationGilbert syndromehyperbilirubinemiaUGT1A1phototherapy |
| spellingShingle | Norman Junge Hanna Hentschel Dorothee Krebs-Schmitt Amelie Stalke Eva-Doreen Pfister Björn Hartleben Martin Claßen Alexander Querfurt Veronika Münch Philip Bufler Jun Oh Enke Grabhorn Mild Crigler–Najjar Syndrome with Progressive Liver Disease—A Multicenter Retrospective Cohort Study Children liver fibrosis liver transplantation Gilbert syndrome hyperbilirubinemia UGT1A1 phototherapy |
| 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 | liver fibrosis liver transplantation Gilbert syndrome hyperbilirubinemia UGT1A1 phototherapy |
| url | https://www.mdpi.com/2227-9067/10/9/1431 |
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