A Philippino glucose-6-phosphate dehydrogenase variant (G6PD Union) with enzyme deficiency and altered substrate specificity.

I NVESTJGATIONS OF RED CELL GLUCOSE-6-PHOSPHATE DEHYDROGENASE ( D-glucose-6-phosphate: NADP oxidoreductase, EC 1.1.1.49; G6PD ) in different human populations have shown that more than 50 variants exist at this time.1’2 Genetic studies are compatible with X-linkage of all G6PD variants. Some variants are associated with normal enzyme activity and therefore are not accompanied by any clinical manifestations ( i.e., G6PD A in Negroes ) . Another group of G6PD variants causes enzyme deficiency but requires exogenous agents such as drugs, infections, or fava beans for hemolysis to occur ( i.e., G6PD A3 and G6PD Mediterranean4 ) . Other variants cause severe instability of the enzyme and are associated with chronic hemolytic disease even in the absence of exogenous agents ( i.e., G6PD Chicago,5 G6PD Oklahoma6 ) . Some variants have an altered substrate specificity ( i.e., G6PD Mediterranean,4 G6PD Markham7). A new G6PD variant with red cell enzyme deficiency and altered substrate specificity was found in a Philippino male and in his relatives. The G6PD deficient brother of the propositus was married to a woman heterozygous for G6PD deficiency. The ancestors of this couple came from the same town, Naguilian of the province La Union, but there was no known consanguinity. The enzyme of the G6PD deficient sons and of one apparently homozygous daughter of this mating ( Fig. 1 ) were studied and were found to have electrophoretic and enzymologic characteristics identical to those found in the index case. The genetic pattern was consistent with X-linked inheritance. The variant was designated as G6PD Union according to the World Health Organization’s recommendations on nomenclature.8