UGT1A1-related Bilirubin Encephalopathy/Kernicterus in Adults

BACKGROUND AND AIMS: Bilirubin encephalopathy/kernicterus is very rare in adults. This study is aimed to investigate the clinical manifestations and genetic features of two patients with UGT1A1-related kernicterus. METHODS: Sanger sequencing analysis was performed to identify UGT1A1 gene mutations in the patients and their families. Bioinformatics analysis was used to predict the potential functional effects of novel missense mutations. Clinical manifestations and biochemical parameters were collected and analyzed. RESULTS: Two patients with Crigler-Najjar syndrome type II (CNS2) developed kernicterus in adulthood. Sanger sequencing identified a compound heterozygous mutation in the UGT1A1 gene in patient 1, which was inherited from his mother (G71R) and his father (c.-3279T>G; S191F). Patient 2 carried three heterozygous mutations, namely G71R, R209W and M391K; among which, the M391K mutation has not been reported before. Multiple prediction software showed that the M391K mutation was pathogenic. Symptoms were relieved in the two patients after phenobarbital and artificial liver support treatment. Patient 1 also underwent liver transplantation. CONCLUSIONS: Adults with CNS2 are at risk for kernicterus. Phenobarbital treatment is beneficial for maintaining bilirubin levels and preventing kernicterus.