A Philippino Glucose-6-Phosphate Dehydrogenase Variant (G6PD Union) With Enzyme Deficiency and Altered Substrate Specificity

Abstract

Abstract A variant of glucose-6-phosphate dehydrogenase (G6PD) associated with altered substrate specificity and severe deficiency of red cell enzyme activity was found in a Philippino male and in his relatives. The genetic pattern was consistent with X-linked inheritance. α-Thalassemia was found in the propositus and in several family members, but there was no interaction between G6PD deficiency and α-thalassemia. This G6PD variant has two pH optima, at pH 5.5 and pH 9.0, while the normal enzyme is inactive at pH 5.5. The substrate specificity of the variant enzyme is different from any known G6PD variant: 2-deoxyglucose-6-phosphate and galactose-6-phosphate are good substrates and deamino-NADP is a better coenzyme than NADP. Although G6PD activity in the variant red cells was only three per cent of normal, quantitative immunologic neutralization suggested that the specific activity of the variant enzyme might be at least ten per cent of that of the normal enzyme. This variant is named after the place of origin, Gd Union.