Publication:

A rare case of Crigler–Najjar syndrome type II in a preterm infant: clinical, genetic and therapeutic insights into the UGT1A1 Pro176Leu variant

Crigler–Najjar syndrome type II is a rare autosomal recessive disorder caused by partial deficiency of uridine diphosphate-glucuronosyltransferase (UGT1A1), resulting in unconjugated hyperbilirubinemia. Differentiating Crigler–Najjar syndrome type II from common neonatal jaundice can be challenging, particularly in premature infants, yet early diagnosis is critical to prevent bilirubin-induced neurotoxicity. We report a 32-week preterm male neonate presenting with progressive jaundice, with peak total serum bilirubin reaching 24 mg/dl. Hemolysis and hepatic dysfunction were excluded through laboratory evaluation. Genetic analysis was performed to identify underlying enzymatic defects. The infant was managed with intensive blue-light phototherapy and phenobarbital at a dose of 5 mg/kg/day, with serial bilirubin monitoring. Genetic testing demonstrated a homozygous UGT1A1 Pro176Leu mutation, confirming Crigler–Najjar syndrome type II. Following initiation of therapy, serum bilirubin levels declined by approximately 25% within one week, consistent with typical Crigler–Najjar syndrome type II responsiveness to phenobarbital. The neonate exhibited no clinical features of kernicterus, and bilirubin levels stabilized below 15 mg/dl by day 12 of life. This case underscores the diagnostic difficulty of distinguishing Crigler–Najjar syndrome type II from physiological or prematurity-related jaundice. Identification of the rarely reported Pro176Leu variant in a preterm neonate provides additional genetic and developmental insight. Early recognition, prompt initiation of phototherapy, phenobarbital therapy, and caregiver education remain essential to prevent bilirubin-induced neurological injury.