Mild Crigler-Najjar Syndrome with Progressive Liver Disease-A Multicenter Retrospective Cohort Study

TY - JOUR

T1 - Mild Crigler-Najjar Syndrome with Progressive Liver Disease-A Multicenter Retrospective Cohort Study

AU - Junge, Norman

AU - Hentschel, Hanna

AU - Krebs-Schmitt, Dorothee

AU - Stalke, Amelie

AU - Pfister, Eva-Doreen

AU - Hartleben, Björn

AU - Claßen, Martin

AU - Querfurt, Alexander

AU - Münch, Veronika

AU - Bufler, Philip

AU - Oh, Jun

AU - Grabhorn, Enke

PY - 2023/8/22

Y1 - 2023/8/22

N2 - 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.

AB - 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.

U2 - 10.3390/children10091431

DO - 10.3390/children10091431

M3 - SCORING: Journal article

C2 - 37761392

VL - 10

JO - CHILDREN-BASEL

JF - CHILDREN-BASEL

SN - 2227-9067

IS - 9

M1 - 1431

ER -