Two new glucose 6-phosphate dehydrogenase variants associated with congenital nonspherocytic hemolytic anemia found in Japan: Gd(-) tokushima and gd(-) tokyo

Abstract

Two new variants of glucose 6‐phosphate dehydrogenase (G6PD) deficiency associated with chronic nonspherocytic hemolytic anemia were discovered in Japan. Gd(‐) Tokushima was found in a 17‐year‐old male whose erythrocytes contained 4.4% of normal enzyme activity. Partially purified enzyme revealed a main band of normal electrophoretic mobility with additional two minor bands of different mobility; normal Km G6P, and Km NADP five‐ to sixfold higher than normal; normal utilization of 2‐deoxy‐G6P, galactose‐6P, and deamino‐NADP; marked thermal instability; a normal pH curve; and normal Ki NADPH. The hemolytic anemia was moderate to severe. Gd(‐) Tokyo was characterized from a 15‐year‐old male who had chronic nonspherocytic hemolytic anemia of mild degree. The erythrocytes contained 3% of normal enzyme activity, and partially purified enzyme revealed slow electrophoretic mobility (90% of normal for both a tris‐hydrochloride buffer system and a tris‐EDTA‐borate buffer system, and 70% of normal for a phosphate buffer system); normal Km G6P and Km NADP; normal utilization of 2‐deoxy‐G6P, galactose‐6P, and deamino‐NADP; greatly increased thermal instability; a normal pH curve; and normal Ki NADPH. These two variants are clearly different from hitherto described G6PD variants, including the Japanese variants Gd(‐) Heian and Gd(‐) Kyoto. The mothers of both Gd(‐) Tokushima and Gd(‐) Tokyo were found to be heterozygote by an ascorbate‐cyanide test.