Background and Aims The G6PD gene mutation is associated with the development of neonatal hyperbilirubinaemia in Asian infants. The c.211G>A mutation of the UGT1A1 gene may contribute but the clinical significance and impact of a combination of these mutations have not been explored. The purpose of this study was to determine whether G6PD and UGT1A1 mutations together, were associated with significant neonatal hyperbilirubinaemia.

Methods Venous blood samples were collected from newborn infants monitored for jaundice and from non-jaundiced infants who served as controls. The G6PD and c. 211G>A of UGT1A1 gene mutations commonly reported among Asians were studied. G6PD enzyme measurements were performed using the fluorescent spot test and enzyme activity assay. Significant hyperbilirubinaemia was defined as a total serum bilirubin (TSB) of ≥250 µmol/L.

Results The majority of infants were of Malay (n=256) and Chinese (n=89) descent. The G6PD mutations obtained were c.871G>A (17.4%), c.487G>A (6.3%), c.1376G>T (4%) and c.1388G>A (3%). One in five infants with G6PD deficiency developed significant hyperbilirubinaemia at three days of life. Infants with c.211G>A of UGT1A1 (18.8%) were two times more likely to be associated with significant hyperbilirubinaemia (p=0.026). Even if normal G6PD, the mean TSB among heterozygous/homozygous c.211G>A mutation (291±78 µmol/L) was significantly higher than normal UGT1A1 (241±73 µmol/L)(p=0.014). The limited number of infants showing combined G6PD and UGT1A1 mutations did not impact significantly on hyperbilirubinaemia in this study.

Conclusion c.211G>A UGT1A1 mutation was an independent risk factor, with c.871G>A being the most common G6PD mutation associated with significant hyperbilirubinaemia amongst Malaysian neonates.