An Hereditary Enzymatic Defect in Erythrocyte Metabolism: Glucose-6-Phosphate Dehydrogenase Deficiency1

Abstract

Earlier investigators demonstrated that alterations in glutathione metabolism were present in erythrocytes of patients susceptible to increased hemolysis following ingestion of a variety of chemical agents, and that this defect in erythrocyte glutathione metabolism may be associated with the deficiency in glucose-6-phosphate dehydrogenase (G-6-P.D.) activity. In the present study erythrocyte G-6-P.D. deficiency was encountered in 4.6% of an unselected population of 305 subjects. This enzymatic defect was more common among healthy Negroes (7.2%) than among healthy Caucasians (1.3%). A reduction in this red cell enzyme was detected in individuals with hemolytic anemia history due to naphthalene ingestion and fava bean consumption and of undetermined cause. A decrease in erythrocyte reduced glutathione (GSH) stability upon incubation with acetylphenylhydrazine was consistently associated with a deficiency in G-6-P.D., except in very young infants. Infants under 55 hours of age demonstrated striking instability in GSH despite high levels of G-6-P.D. activity. The present data establish an hereditary basis for the reduction of erythrocyte G-6-P.D. They strongly suggest that the gene responsible for the transmission of this trait is sex-linked and also sex-modified.