Heterogeneity of ?Mediterranean type? glucose-6-phosphate dehydrogenase (G6PD) deficiency in Spain and description of two new variants associated with favism

Abstract

Glucose-6-phosphate dehydrogenase (G6PD); EC 1.1.1.49 from thirty-six unrelated Spanish males was partially purified from blood, and the variants were characterized biochemically and electrophoretically according to the methods recommended by the world Health Organization. Subjects were from multiple geographic regions within Spain, and all suffered from hemolytic anemia, either acute (34 cases) or chronic nonspherocytic (2 cases). Almost all the variants studied presented residual erythrocyte G6PD activity ranging from 0 to 10% of normal, and five different mutants were responsible for the deficient phenotype. Three variants were similar to others previously described: G6PD Mediterranean (11 cases), G6PD Athens-like (3 cases), and G6PD Union (2 cases). The remaining variants were different from the numerous variants already reported and have been considered as new mutants. Provisionally they are called G6PD Betica (19 cases) and G6PD Menorca (1 case). The present study constitutes the first attempt to characterize the deficient G6PD variants found in Spain and supplies new data on the relationship between molecular characteristics of deficient variants and their clinical manifestations. The most important findings can be summarized as follows: (1) The Spanish population is characterized by an important heterogeneity in G6PD deficiency. (2) Although G6PD Mediterranean is very frequent, it presents a relatively high degree of polymorphism. (3) Favism has been observed associated with all kinds of variants described here. (4) G6PD Betica, which is the most frequent variant found in subjects of Southern Spanish origin, has been observed associated with favism in all cases except one.

Genetic Epidemiology of Glucose-6-Phosphate Dehydrogenase Deficiency in the Arab World

“…A comparison between the mutations in Arabs and Asians showed that most of the mutations responsible for the G6PDD shared among the two ethnic groups, which could be due to the long history of admixture among the two ethnic groups. These mutations were also shared with other ethnic groups, for example, the most frequent mutation among Arabs, p.S188F, was also frequently reported in Greece, southern Italy, Spain, Bulgaria, Romania, Turkey, and Israel14151617. We identified the most frequent mutations (p.S188F, p.V68M, p.I48T and p.N126D) and unique mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) circulated among Arabs.…”

Polymorphic sites in the African population detected by sequence analysis of the glucose-6-phosphate dehydrogenase gene outline the evolution of the variants A and A-.

“…(14)], in a sample of G6PD Betica (not shown), which is the same as G6PD A-and is polymorphic in Spain (18), and in samples of G6PD A-from white men from Corsica and North Carolina (T.J.V. and L.L., unpublished), it seems reasonable to assume that it has spread to these places from Africa.…”

Hereditary non‐spherocytic haemolytic anaemia due to red blood cell glutathione synthetase deficiency in four unrelated patients from Spain: clinical and molecular studies

“…It is worth mentioning that in case 3 the diagnosis was established after an episode of acute haemolytic crisis due to fava bean ingestion. Favism, which is the most frequent clinical manifestation of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in Spain (Vives‐Corrons & Pujades, 1982), has also been described in GSH‐S deficiency by Oort et al (1961) and by Mohler et al (1970). Furthermore, the very low GSH content in these patients' RBCs may also explain the higher sensitivity of these cells to oxidative damage, as demonstrated by the increased production of MDA in presence of hydrogen peroxide (H 2 O 2 ).…”