Should We Consider UGT1A1 Mutation Analysis in Evaluating the Prolonged Jaundice of Newborn Infants?

Abstract

Purpose: Uridine diphosphate glucuronosyltransferase 1A isoform 1 (<i>UGT1A1</i>) is a crucial enzyme in bilirubin metabolism. Mutations in this gene cause prolonged unconjugated hyperbilirubinemia in infants. This study aimed to investigate the prevalence of <i>UGT1A1</i> mutations and their association with prolonged, unexplained, and unconjugated hyperbilirubinemia in infants.Methods: From July 2019 to March 2023, 74 infants with prolonged jaundice lasting >21 days were enrolled in this study. Diagnostic evaluations, including <i>UGT1A1</i> mutation analysis, were performed to identify the underlying causes of hyperbilirubinemia. This retrospective review evaluated the incidence and types of mutations in <i>UGT1A1</i>. The clinical and laboratory findings were compared based on the specific mutations detected.Results: Thirty-three infants agreed to <i>UGT1A1</i> mutation analysis, and 30 (90.9%) were positive for <i>UGT1A1</i> mutations. Single-nucleotide variants were detected in 20 (66. %) infants. The remaining 10 (33.3%) infants had multiple variants. No significant demographic differences were observed between the group that underwent <i>UGT1A1</i> mutation analysis and the group that did not. Among the identified genetic variants, c.211G>A (46.5%) and c.-3275T>G (30.2%) were the two most common variants. The other variants had the following percentages: c.1456T>G, c.-64G>C, and c.1091C>T (4.7% each); and c.-3152G>A, c.189C>T, and c.-41.-40 dup (2.3% each). Among the 20 infants with the c.211G>A variant, eight (40.0%) had a homozygous genotype and 12 (60.0%) had a heterozygous genotype. Infants harboring other variants exhibited heterozygous genotypes. When comparing the group with confirmed <i>UGT1A1</i> mutations to the group without detected mutations, breastfeeding was the only significant factor (<i>p</i>=0.027). No significant differences were found between the group with singlenucleotide variants and the group with multiple genetic variants or between the homozygous genotype group with c.211G>A and the heterozygous genotype group.Conclusion: Neonates with prolonged unconjugated hyperbilirubinemia may have a higher chance of <i>UGT1A1</i> mutation than expected. Analysis of <i>UGT1A1</i> mutations may be beneficial in infants with prolonged unexplained jaundice.