Prevalence of Gilbert syndrome in parents of neonates with pathologic indirect hyperbilirubinemia

Abstract

BACKGROUND AND OBJECTIVES:The cause of hyperbilirubinemia cannot be found in about 45% of cases of neonatal jaundice. Gilbert syndrome (GS) is the most common congenital disease associated with bilirubin metabolism in the liver. Since the screening value of genetic tests cannot be fully determined until accurate data on the prevalence and penetrance of the GS genotype are known, we sought to estimate whether the prevalence of GS is higher in the parents of neonates with severe unexplained indirect hyperbilirubinemia.DESIGN AND SETTING:Case-control study of parents of neonates with severe unexplained indirect hyperbilirubinemia admitted to a neonatal ward.METHODS:We used the rifampin test (checked bilirubin before and 4 hours after administration of 600 mg rifampin) for diagnosis of GS in parents of 115 neonates with severe unexplained indirect hyperbilirubinemia. We compared the prevalence of GS in these parents with that of a control group of 115 couples referred for premarital counseling.RESULTS:The 115 neonates were aged 5.2 (1.6) days (mean, standard deviation), all were breast-fed, and males constituted 56.5%. Mean total serum bilirubin (TSB) level was 20.96 (5.48) mg/dL. 14.8% were glucose 6 phosphate dehydrogenase (G6PD) deficiency was present in 14.8%, and 10.4% had A, B or O blood group (ABO) incompatibilities with their mothers. There was no difference in the prevalence of GS between parents of the group with hyperbilirubinemia (22.2%) and the control group (19.13%) (P=.42). Mean TSB in neonates with parents who had GS was more (about 3 mg/dL) than in neonates with normal parents (P=.004). Fathers had GS twice as often as the mothers among the parents of neonates with hyperbilirubinemia (P=.003), among the control group (P=.009) and among neonates (P=.014).CONCLUSION:This study showed that GS cannot cause severe indirect hyperbilirubinemia by itself, but it may have a summative effect on rising bilirubin when combined with other factors, for example, G6PD. Our results showed that in GS, males are affected about twice as much as the females.

Prolonged Jaundice in a Premature Breastfed Infant With Gilbert’s Syndrome

“…For each week of gestation less than 40 weeks, the odds of developing hyperbilirubinemia increase by a factor of 1.7 (Flaherman et al, 2017). In 45% of the cases of neonatal jaundice, the cause of hyperbilirubinemia is unknown (Saki et al, 2011).…”

“…The relationship between prolonged jaundice in breastfed infants and Gilbert’s syndrome is presented in only a few earlier case studies and there is limited literature that explores the topic (Bancroft et al, 1998; Hong et al, 2010 ; Maruo et al, 2000 ; Monaghan et al, 1999 ; Saki et al, 2011 ). This case study describes the diagnostic and therapeutic challenges associated with Gilbert’s syndrome in a late premature breastfed infant living in Germany.…”

“…Gilbert’s Syndrome is the most common hereditary congenital disorder resulting in increased levels of unconjugated bilirubin in the bloodstream ( Saki et al, 2011 ). GS is caused by a mutation in the UGT1A1 gene which results in decreased activity of the uridine diphosphate-glucuronosyltransferase (UGT) enzyme.…”

“…The main role of UGT is to detoxify bilirubin by conjugating it with glucuronic acid ( Hong et al, 2010 ). GS alone cannot cause severe indirect hyperbilirubinemia, but may have a summative effect on bilirubin levels when combined with other factors like Glucose 6 phosphate dehydrogenase (G6PD) deficiency ( Saki et al, 2011 ). GS alone does not require a secondary care referral, is largely asymptomatic, and does not influence life expectancy ( King & Armstrong, 2019 ).…”