A recent study of 170 Japanese infants with breast milk jaundice (BMJ) demonstrated that 52% had a homozygous mutation: UGT1A1*6 (J Pediatr 2014; 165: 36-41). The study included 55 controls without BMJ.
Defects in UGT1A1 have been associated with a number of hereditary unconjugated hyperbilirubinemias including Crigler-Najjar type 1 in which there is complete deficiency of the enzyme Crigler-Najjar type 2 in which there is limited activity of the enzyme, and Gilbert syndrome in which there is moderate activity of the enzyme (but less than general population).
In this study, none of the control population had the UGT1A1*6 homozygous mutation. The authors note that “the components of breast milk clearly contribute to the onset of neonatal jaundice. Our in vitro investigation showed the inhibitory effect of 5α-pregnane-3α, 20β-diol on UGT1A1 activity.” Thus, this may help explain why cessation of breastfeeding for a short period can improve BMJ.
Take-home message: In this Japanese population, the UGT1A1*6 homozygous mutation is an important reason for BMJ. Yet, for about half of all infants another, yet unidentified mechanism(s), is responsible.