Selective occurrence of glutathione instability in red blood corpuscles of the various Jewish tribes.

By A. SZEINBERG, CH. SHEBA AND A. ADAM W E EMBARKED ON THE STUDY of hematologic differences between Ashkenazic and non-Ashkenazic Jews#{176}when it was certain that only the latter were victims of hemolysis due to known (Vicia faba, sulpha drugs) or unknown (bacterial, viral?) noxious agents. We assumed the existence of a familial inherited trait of the red blood corpuscle, in addition to which a known or unknown trigger mechanism is required to prodtice hemolysis.1 We did not possess any laboratory tool for confirmation or elucidation of this difference between erythrocytes of the two branches of exiles, those from “Judea capta” 70 A.D. and those from Judea, first destroyed in 586 B.C. by the Babylonians. The enzymatic abnormalities found in Negroes susceptible to hemolysis following administration of primaquine2’3 directed us to the search of these chemical deviations in our patient material. Our search was rewarded by the confirmation of glutathione deficiency and glutathione instability in the erythrocytes of all cases of favism and drug-induced hemolytic anemia.4#{176} We also found proof of familial occtirrence of these abnormalities, but the material was not large enough to form a final opinion on the genetic pattern of transmission. Meanwhile, important progress has been achieved abroad in the study of the erythrocyte abnormality and its connection with susceptibility to hemolysis in other population groups. Carson et al. and Schrier et al. discovered two enzymatic abnormalities in the erythrocytes of primaquine-sensitive American Negroes, namely, a deficient glucose-6-phosphate dehydrogenase activity and increased glutathione reductase activity.79 Kimbro et al. described cases of hemolytic anemia induced by nitrofurantoin in subjects with instable GSH and proved that, in vitro, this drug has a similar effect to acetyl phenyl hydrazine upon glutathione stability. They reported that random screening of a large group of Negro subjects revealed 7.8 per cent incidence of the intrinsic RBC abnormality with a predominant occurrence in males.10’1’ Browne sttidied the inheritance pattern of this abnormality in American Negroes and suggested transmission by a sex-linked gene of intermediate dominance. Males with the abnormal gene and homozygous females were postulated to he drug sensitive.12 Zinkham and Childs have shown that hemolytic anemia caused by naphtalene occurs foremost in individuals with the same erythrocyte abnormality. They also found that though naphtalene does not influence in vitro GSH stability, its metabolities such as alpha and beta naphtol have an effect similar to acetyl phenyl hydrazine. An additional finding of prime importance