A novel UGT1A1 gene mutation causing severe unconjugated hyperbilirubinemia: a case report.

ABSTRACT:

Background

Crigler-Najjar syndrome (CNs) presents as unconjugated hyperbilirubinemia, as a result of UGT1A1 deficiency, and can be categorized in a severe (type I) and mild (type II) phenotype. CNs type II patients usually benefit from phenobarbital treatment that induces residual UGT1A1 activity.

Case presentation

Here we present a CNs type II patient that is not responsive to phenobarbital treatment, which can be explained by two heterozygous mutations in the UGT1A1 gene. A 3 nucleotide insertion in the HNF-1? binding site in the proximal promoter previously reported in a Crigler-Najjar patient on one allele and a novel two nucleotide deletion in exon 1, resulting in a frameshift and a premature stop codon.

Conclusion

In newly diagnosed CNs patients with unconjugated bilirubin levels consistent with CNs type II but that are unresponsive to phenobarbital treatment, disruption of the HNF-1? binding site in the proximal promoter should be considered as a probable cause. Upon confirming a mutation in the HNF-1? site, phenobarbital treatment should be stopped or at least be reconsidered because of its sedative effects and its teratogenic properties.

SUBMITTER: Shi X 

PROVIDER: S-EPMC6540546 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature