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

• Main Authors: Xiaoxia Shi, Sem Aronson, Ahmed Sharif Khan, Piter J. Bosma
• Format: Article
• Language: English
• Published: BMC 2019-05-01
• Series: BMC Pediatrics
• Subjects: Crigler-Najjar syndrome; UGT1A1; HNF-1α; Genetic analysis
• Online Access: http://link.springer.com/article/10.1186/s12887-019-1555-y

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-1α 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-1α binding site in the proximal promoter should be considered as a probable cause. Upon confirming a mutation in the HNF-1α site, phenobarbital treatment should be stopped or at least be reconsidered because of its sedative effects and its teratogenic properties.