Glucose-6-Phosphate Dehydrogenase (G6PD) African A− Variant and Clinical Severity of Homozygous Sickle Cell Disease: A Prospective Descriptive Study

Abstract Background: Some investigators observed that glucose-6-phosphate dehydrogenase (G6PD) deficiency increases the severity of sickle cell disease (SCD); others found no such effects. The variable findings could be because SCD includes different genetic entities, and different mutants of the G6PD gene cause varying degrees of enzyme deficiency. Objective: The objective of this study was to describe the features of SCD in homozygous (HbSS) patients confirmed by DNA sequencing to have the specific mutant gene G6PD African Minus ( A − ; 202G>A; 376A>G), and homozygosity for G A G => G T G mutation in codon 7 of the beta-globin gene ( HBB ), which causes homozygous SCD. Materials and Methods: In this prospective descriptive study, DNA from 36 HbSS patients (17 males and 19 females; age 12–40 years) diagnosed by high-performance liquid chromatography was sequenced to confirm homozygosity for the G A G => G T G mutation in HBB , and identify individuals with co-existent G6PD A − gene. Features of SCD in these individuals were described. Results: DNA sequencing confirmed homozygosity for HBB seventh codon G A G => G T G mutation in all patients, and detected the mutant G6PD A − gene in three individuals. All three had avascular necrosis of the femoral head with other features of severe SCD: severe thrombocytosis (platelet count: 527 × 10 9 /L) and vaso-occlusive crisis in the first; cortical blindness, seizures, meningitis, severe vaso-occlusive crisis in the second; severe anemia during steady state (hemoglobin: 3.6 g/dL), frequent blood transfusions, and chronic osteomyelitis in the third. Conclusion: The G6PD African A − variant was identified in three patients with homozygous SCD, all of whom had severe clinical manifestations. These findings suggest a possible association between the G6PD A − variant and severe SCD phenotypes; however, the small number of affected individuals and absence of a comparative group preclude conclusions regarding a modifying effect. Larger comparative studies are needed to clarify the clinical significance of this variant in SCD.