Avinoam Adam

A STUDY OF SUBJECTS WITH ERYTHROCYTE GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY: INVESTIGATION OF PLATELET ENZYMES*

A hereditary abnormality of the erythrocytes was described in Negroes sensitive to primaquine (1). A similar or identical defect has been detected in the erythrocytes of a considerable proportion of non-Ashkenazic Jews susceptible to favism and sensitive to various drugs (2-4). The primary defect of these erythrocytes is probably the markedly decreased activity of glucose6-phosphate dehydrogenase (5). The cells, however, demonstrate a multitude of secondary abnormalities, namely: a low glutathione (GSH) level; glutathione instability; a decreased glycine incorporation rate into GSHin vitro; and an increase in glutathione reductase, aldolase and triphosphopyridine nucleotide (6-9). This hereditary erythrocyte defect is transmitted probably as a sex-linked incompletely dominant trait with various degrees of expressivity of the abnormal gene in affected females (3, 10). In view of the importance of the hexose monophosphate shunt in glucose metabolism in various tissues and the key role of glucose-6-phosphate dehydrogenase in this metabolic pathway, it is of great interest to determine whether this genetic defect of the erythrocytes is demonstrable in other tissues of the affected subjects. In the present communication we describe the results of an investigation of glucose-6-phosphate dehydrogenase activity in platelets of normal and affected individuals.

Epidemiologic Surveys of Deleterious Genes in Different Population Groups in Israel

THE geographic distribution of genetic traits of human populations is influenced by many factors, the most important of which are (in the light of the present knowledge) the ethnic origin of the population, the degree of its isolation and the rate of consanguineous marriages, and the environmental conditions acting upon the advantageous or the detrimental selective values of the traits. The contemporary Jewish community of Israel presents a unique opportunity for gathering important data for the study of these factors. The Jewish people, who were dispersed for 20-25 centuries throughout wide geographic areas and lived among different ethnic groups, gathered in Israel during the last 50 years, and particularly within the last decade. During the long period of dispersal strong religious and cultural bonds enabled the Jewish communities in the Diaspora to survive, preventing their assimilation among the local populations. The inferior social status which they occupied in many countries, as well as the enmity toward their religion, prevented in most cases a large-scale influx Bracha Ramot, M.D.; Avinoam Adam, M.Sc.;

Data for X-mapping calculations, Israeli families tested for Xg, g-6-pd and for colour vision

The results are recorded of tests for the X‐linked red cell antigen Xga on families with glucose‐6‐phosphate dehydrogenase deficient members. The families live in Israel and belong to Kurdish, Iraqi, Yemenite, Sefardic and Ashkenazy Communities.

Linkage relations of X‐borne ichthyosis to the Xg blood groups and to other markers of the X in Israelis

A series of families in the counties around Oxford (Kerr, Wells & Sanger, 1964) gave the first indication that there was reasonably close linkage between the Xg blood groups and the X-borne type of ichthyosis. This stimulated the investigation in Israel of which the present paper gives the full account (it includes the data of an interim report by Adam et al. 1966). The Oxford findings also stimulated a survey based on London (Wells et al. 1966). These three publications established beyond any doubt that the locus for Xg is close to that for ichthyosis. The survey in Israel included tests for glucose-6-phosphate dehydrogenase (g-6-pd) aa well as for colour vision.

Glucose-6-Phosphate Dehydrogenase Deficiency and Haemolytic Disease of the Newborn in Israel

Recent reports from Sardinia, Greece and Malaya indicate that glucose-6phosphate dehydrogenase (G-6PD) deficiency may constitute an important aetiological factor in the causation of severe neonatal jaundice and kernikterus (Panizon, 1960a, b; Doxiadis, Fessas and Valaes, 1961; Smith and Vella, 1960; Weatherall, 1960). Since this enzyme deficiency is very frequent in certain oriental Jewish communities in Israel (Szeinberg, Sheba and Adam, 1958; Sheba, Szeinberg, Ramot, Adam and Ashkenazi, 1962), a high incidence of severe jaundice of newborn not due to iso-immunization could be expected to occur in this country. If this were the case, a considerable disadvantage to carriers of this trait, even under natural conditions (without intake of drugs), would have to be assumed. From the practical point of view such a finding would necessitate the establishment of large-scale facilities for exchange transfusion in the areas inhabited by population groups with a high frequency of G-6PD deficiency. A preliminary inquiry among paediatricians in several hospitals did not reveal any awareness of a difference in frequency of severe jaundice and transfusions between Oriental and European (Ashkenazi) Jewish communities. However, in view of the findings in other countries listed above, we decided to investigate this problem more closely.t

The incorporation of isotopically labelled glycine into glutathione of erythrocytes with glucose-6-phosphate dehydrogenase deficiency

Abstract 1. 1. Cysteine decreases the reduced glutathione level in normal red blood cells incubated under aerobic conditions in a glucose-free incubation medium. 2. 2. Cysteine has a similar effect in cells deficient in glucose-6-phosphate dehydrogenase, even in the presence of glucose. 3. 3. Investigations of the rate of glycine incorporation into glutathione of normal erythrocytes under aerobic conditions should be conducted in the presence of glucose when the incubation mixture contains cysteine. The glucose may be replaced by fructose, galactose or inosine. Cysteine should be omitted altogether from the incubation mixture when cells deficient in glucose-6-phosphate dehydrogenase are investigated. 4. 4. The rate of incorporation of glycine into glutathione in deficient cells was found to be lower than in normal cells. The possible causes of this difference are discussed.

The linkage relation of Xg to g‐6‐pd in Israelis: the evidence of a second series of families

The loci for Xg and for glucose‐6‐phosphate dehydrogenase are not within direct measurable distance of each other. Analysis of two‐generation data for a previous series of Israeli families strongly suggested that linkage was measurable, but massive three‐generation data from Sardinia contradicted this and stimulated the collection of a second series in Israel, this time confined mostly to three‐generation families. The two Israeli series combined now agree with the Sardinian series in showing no evidence of direct measurable linkage.