Fatal Kernicterus in a Girl Deficient in Glucose-6-Phosphate Dehydrogenase: A Paradigm of Synergistic Heterozygosity

A 6-day-old female newborn, readmitted for extreme hyperbilirubinemia with bilirubin encephalopathy, died despite 2 double-volume exchange transfusions. On autopsy examination the basal ganglia and hippocampus were selectively stained deep yellow. The infant was heterozygous for both the glucose-6-phosphate dehydrogenase Mediterranean mutation and for the (TA) 6 /(TA) 7 promoter polymorphism for the gene encoding the bilirubin conjugating enzyme uridine diphosphate–glucuronosyltransferase 1A1 ( UGT1A1*28 , associated with Gilbert syndrome). No additional mutations of the UGT1A1 were detected. Seemingly innocuous, heterozygotic mutations may interact synergistically to result in serious and even fatal outcomes.