DOI: 10.4103/ijmh.ijmh_268_25 ISSN: 2635-3695

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

Osita Ezenwosu, Chinedu A. Ezekekwu, Ebele D. Muoghalu, Kelechi Urom, Ikechukwu O. Anigbogu, Gladys Ilechukwu, Helen C. Okoye, Chukwudi Anigbo, Augustine N. Duru, Uchechukwu J. Aroh, Anita T. Kemuel, Charles C. Nonyelu, Onochie Obodo, Iheanyi Okpala
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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.

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