Glucose-6-Phosphate Dehydrogenase Deficiency: A Worldwide Potential Cause of Severe Neonatal Hyperbilirubinemia

Abstract

After completing this article, readers should be able to: 1. Explain methods of preventing the hyperbilirubinemia caused by glucose-6-phosphate dehydrogenase (G6PD) deficiency. 2. Compare and contrast the correlation between hemolysis and serum bilirubin levels in healthy infants and those who are G6PD-deficient. 3. Describe the role of deficient bilirubin conjugation in the pathogenesis of G6PD deficiency-associated neonatal hyperbilirubinemia. 4. Define the risk for neonatal hyperbilirubinemia in female G6PD-deficient heterozygotes, G6PD-deficient homozygotes, and hemizygote males. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a commonly occurring X-linked genetic enzyme defect, is notorious for its association with acute hemolytic crises occurring in response to a frequently identifiable trigger (favism). Another potentially devastating danger of this condition is severe neonatal hyperbilirubinemia with its accompanying bilirubin encephalopathy, kernicterus, and death. Far from being a condition limited to historical time epochs and developing countries, G6PD deficiency-associated kernicterus still is seen in modern times. Indeed, among 80 infants from 21 states in the United States documented in a pilot Kernicterus Registry between 1984 and 1998, 18 (22.5%) were reported to have G6PD deficiency. Furthermore, Maisels recently listed G6PD deficiency among the 10 factors that are associated most commonly with an increased risk of nonhemolytic jaundice. Because of the association with favism, G6PD-associated hyperbilirubinemia traditionally has been regarded as hemolytic in origin. However, recent research has shown that although acute hemolysis does play a role, its contribution in many cases may be smaller than previously thought. The emphasis now has been placed on decreased bilirubin conjugation, with promoter polymorphism for the gene for the bilirubin conjugating enzyme, UDP glucuronoslytransferase 1A1 (UGT1A1), being a major factor in production of the icterus. In this review we highlight key aspects of the pathogenesis of this type of hyperbilirubinemia, explain the relevance of the condition, and describe a particularly problematic group that has a recently recognized high incidence of …