The Genetics of Glucose-6-Phosphate-Dehydrogenase (G6PD) and Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) Promoter Gene Polymorphism in Relation to Quantitative Biochemical G6PD Activity Measurement and Neonatal Hyperbilirubinemia.

UNLABELLED

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and polymorphism in uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) were associated with significant neonatal hyperbilirubinemia (NHB) and increased risk for kernicterus. However, quantitative screening tests for G6PD enzyme activity proved unsatisfactory in estimating the risk for significant NHB, especially in heterozygous females that could present phenotype overlap between normal homozygotes, heterozygotes, and deficient homozygotes, resulting in a continuum of intermediate G6PD activity.

OBJECTIVE

To examine the association of genotype and phenotype in newborns with decreased G6PD activity and its relation to NHB.

STUDY DESIGN

Quantitative G6PD enzyme activities were measured on umbilical cord blood samples. After accepting parental consent, samples were analyzed for mutations and gene polymorphisms (number of TA repeats in the UGT1A1 promoter). The associations to quantitative G6PD activity and bilirubin levels were assessed.

RESULTS

28 females and 27 males were studied. The mutation () was responsible for most cases of G6PD deficiency (20 hemizygous males, 3 homozygous and 16 heterozygous females). The association between this mutation, decreased G6PD activity and higher bilirubin levels was confirmed. Heterozygosity to 6/7 TA repeats in the promoter was associated with increased NHB, especially in female newborns with G6PD deficiency. However, it seems that the interaction between G6PD deficiency, promoter polymorphism, and NHB is more complex, possibly involving other genetic interactions, not yet described. Despite genotyping females with G6PD deficiency, the overlap between the upper range of borderline and the lower range of normal G6PD activity could not be resolved.

CONCLUSIONS

The results of this study highlight the possibility for future implementation of molecular genetic screening to identify infants at risk for significant NHB, especially polymorphism in heterozygous females with borderline G6PD deficiency. However, further studies are needed before such screening could be applicable to daily practice.