Genetic heterogeneity of glucose 6-phosphate dehydrogenase deficiency in Sardinia

Abstract

Glucose 6-phosphate dehydrogenase (G6PD) activity was assayed quantitatively in red cells from 100 consecutive G6PD-deficient newborn male babies born in a city hospital in Sassari, Sardinia. In four cases G6PD activity was between 30% and 45% of normal: these appeared on electrophoresis to be identical with G6PD Seattle-like. In 65 cases G6PD activity ranged from 2% to 14% of normal, while in the remaining 31 samples no activity could be detected in crude hemolysates. G6PD was partiall purified from 39 samples having activity below 14% of normal (including 20 with zero activity). G6PD activity could now be determined in all, and it was fully characterized in nine samples. These were shown to belong to two distinct classes on grounds of the Michaelis constant for glucose 6-phosphate and the elution profile from DEAE-Sephadex columns. These properties were compared with those of G6PD-deficient samples from Greece and from Israel. We conclude that there are at least three polymorphic G6PD-deficient variants in Northern Sardinia: G6PD Seattle-like, G6PD Mediterranean, and a new variant, which we designate G6PD Sassari. The GdMediterranean and GdSassari genes have been shown to breed true in family studies. We also produce evidence that the definition of G6PD Mediterranean must be carefully reassessed.