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-years-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(-) Tokoyo were found to be heterozygote by an ascorbate-cyanide test.

Molecular abnormality of a Japanese glucose-6-phosphate dehydrogenase variant (G6PD Tokyo) associated with hereditary non-spherocytic hemolytic anemia

“…A case report of the patient and the enzymological properties of the variant enzyme have been published elsewhere (Miwa et al 1976). …”

G6PD Kanazawa: A New Variant of Glucose-6-Phosphate Dehydrogenase Associated with Congenital Nonspherocytic Hemolytic Anemia

“…Cornell [10] and Tokushima [11] have a substantially in creased K," for NADP, and Englewood [12] has a decreased Km for NADP, a finding that is not present in our mutant. Bat Yam [13], Bangkok [14], Boston [15], New York [12], Hayem [16], Hamburg [17] and Dub lin [18] show the marked increase in the uti lization of 2-deoxy-G6P.…”

Several mutations including two novel mutations of the glucose-6-phosphate dehydrogenase gene in Polish G6PD deficient subjects with chronic nonspherocytic hemolytic anemia, acute hemolytic anemia, and favism

“…G6PD Tokyo was described by Miwa et al [1976]. A G to A substitution at nt 1246 was later found by Hirono et al [1992] in the same patient.…”