G-6-PD Manchester: a new variant associated with chronic nonspherocytic hemolytic anemia.

A variant of glucose-6-phosphate dehydrovariant is the slowest yet described. genase (G-6-PD) designated G-6-PD Substrate specificity is normal but enzyme Manchester, and associated with chronic activity is markedly inhibited by NADPH, nonspherocytic hemolytic anemia. was and this is thought to account for the severe found in an English male. The electrochronic hemolysis. phoretic mobility at pH 7.0 of this G-6-PD T HE NUMBER OF different types of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP oxidoreductase, E.C. 1 . I . 1 .49, G-6-PD), which have been described in man is now in the region of 80 different variant enzymes.’ Many of these are not associated with a hemolytic process, either chronic or under the stress ofcertain drugs or chemicals. The first case ofa G-6-PD variant associated with chronic nonspherocytic hemolytic anemia was reported by Newton in 1958.2 Since then about 20 such variants have been described.’ Detailed studies of individual enzyme variants may reveal the biochemical basis for the shortening of the red cell lifespan in vivo. Thus there may be altered enzyme affinity for the substrate glucose-6-phosphate (G-6-P) or coenzyme, NADP, e.g., G-6-PD Oklahoma,3 or there may be instability of the enzyme, e.g., G-6-PD Alhambra.4 The correlation between clinical severity and impairment of enzyme activity, as measured by usual assay methods, is not always close and may sometimes be related to use of unphysiologic concentrations of substrates in the assay system. We now report a new variant, designated G-6-PD Manchester, which gives rise to a severe chronic hemolytic anemia, but where enzyme activity by standard assay is only moderately reduced.