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

• Published in: BMC pediatrics Vol. 19; no. 1; p. 173
• Main Authors: Shi, Xiaoxia, Aronson, Sem, Khan, Ahmed Sharif, Bosma, Piter J
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.05.2019; BioMed Central; BMC
• Subjects: Bilirubin; Binding sites; Care and treatment; Case Report; Case reports; Codons; Crigler-Najjar syndrome; Enzymes; Gene mutation; Genes; Genetic analysis; Genetic aspects; Genetic research; Hemoglobin; HNF-1α; Hyperbilirubinemia; Liver; Metabolism; Mutation; Novels; Parents & parenting; Pediatric research; Phenobarbital; Probable cause; Promoters (Genetics); UGT1A1; Crigler-Najjar syndrome; UGT1A1; HNF-1α; Genetic analysis
• ISSN: 1471-2431; 1471-2431
• DOI: 10.1186/s12887-019-1555-y

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. 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. 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.