Lessons from the molecular biology of neonatal hyperbilirubinaemia

Compared to Caucasians, South East Asian babies have more frequently jaundice, requiring phototherapy. This is partly due to the high prevalence of G6PD deficiency and other genetically determined haematological abnormalities. If no underlying cause is found, these babies tend to be labelled as having 'excessive' physiological jaundice or alternatively idiopathic pathological jaundice. It is likely however that jaundice in newborns is a complex interplay between multiple genetic and environmental risk factors. Often more than one risk factor may be present such as in G6PD deficiency where recently it was discovered that neonatal jaundice is often only not accompanied by haemolysis. An association was found with Gilbert syndrome. One relatively recently described risk factor in the South East Asian population is the presence of point mutations in the coding regions for the gene of the uridine diphosphate glucuronyl transferase enzyme. These point mutations may decrease the activity of the enzyme responsible for glucuronidation of the indirect bilirubin just slightly. This can cause jaundice that is really excessive in babies with other risk factors. Neonatal jaundice is most likely a real multifactorial pathological event based on many genetic and environmental factors. In future we will look more at a combination of risk factors for jaundice, rather than just attributing the jaundice to one risk factor alone. The number of babies labelled as 'excessive physiologic jaundice' or idiopathic jaundice might decrease significantly in the near future.