Severe neonatal hyperbilirubinaemia in preterm twins with glucose-6-phosphate dehydrogenase deficiency and UGT1A1 gene variants

Neonatal unconjugated hyperbilirubinaemia may have a multifactorial aetiology, and different conditions may act together to increase the risk of severe hyperbilirubinaemia and bilirubin-induced neurological dysfunction. We report a novel case of severe neonatal unconjugated hyperbilirubinaemia requiring treatment with exchange transfusions in two premature twins with a similar clinical presentation. The aetiological investigation revealed glucose-6-phosphate dehydrogenase (G6PD) deficiency combined with heterozygosity for two variants in the UGT1A1 gene. These two conditions alone are common genetic causes of neonatal hyperbilirubinaemia, but the co-occurrence of both in the same patient is unusual. This case highlights a rare synergistic interaction between preterm birth, G6PD deficiency and UGT1A1 variants in the development of a severe case of neonatal unconjugated hyperbilirubinaemia in the absence of identifiable haemolysis.