Summary
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.
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References
Ben Bassat J, Ben-Ishay D (1969) Hereditary hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency (Mediterranean type). Isr J Med Sci 5:1053–1059
Betke K, Beutler E, Brewer GJ, Kirkman HN, Luzzato L, Motulsky AG, Ramot B, Siniscalco M (1967) Standardization of procedures for the study of glucose-6-phosphate dehydrogenase. Report of a WHO Scientific Group. WHO Tech Rep Ser 366
Beutler E (1978) Hemolytic anemia in disorders of red cell metabolism. In: Topics in hematology. Plenum Medical Book Company, New York London, pp 23–167
Beutler E, Mathai CK, Smith JE (1968) Biochemical variants of glucose-6-phosphate dehydrogenase giving rise to congenital nonspherocytic hemolytic disease. Blood 31:131–150
Bøyum A (1974) Separation of blood leukocytes, granulocytes and lymphocytes. Tissue Antigens 4:269
Dacie JV, Lewis SM (1975) Practical haematology, 5th ed. Churchill, Livingstone
Dacie JV, Grimes AJ, Meisler A, Stengold L, Hemsted EA, Beaven GH, White JC (1969) Hereditary Heinz-body hemolytic anemia. A report of studies of five patients with mild anemia. Br J Haematol 10:388–394
Flatz G, Duren P (1967) Glucose-6-phosphate dehydrogenase deficiency in Spain. Hum Genet 4:81–83
Gherardi G, Bierme R, Corberand J, Pris J, Vergnes H (1976) Distribution of G6PD types in the populations of Southwest France: Common variants and new variants. Hum Hered 26:279–289
Gherardi M, Vergnes H, Rochiccioli P, Duteau G (1972) Gd(-) A variant of glucose-6-phosphate dehydrogenase in an Algerian family. Enzyme 13:293–304
Goedde HW, Hirth J, Benkmann HC, Pellicer A, Pellicer T, Stahn M, Singh S (1972) Population genetic studies of red cell enzyme polymorphism in four Spanish populations. Hum Hered 22:552–560
Grimes AJ (1980) Human red cell metabolism. Blackwell Scientific Publications, Oxford, pp 239–258
Kahn A, Cottreau D, Boivin P (1974) Molecular mechanism of glucose-6-phosphate dehydrogenase deficiency. Hum Genet 25:101–109
Kaplan JC, Rosa R, Sevinge P, Hoeffel JC (1976) La polymorphisme genetique de la glucose 6-phosphate dehydrogenase erythrocytaire chez l'homme. Etude d'une nouvelle variante à activité diminuee: Le type «Kabyle». Enzyme Biol Clin 8:332–340
Kirkman HN, Schettini F, Pickard BM (1964) Mediterranean variant of glucose 6-phosphate dehydrogenase. J Lab Clin Med 63:726–735
Kirkman HN, Dioxiadis SA, Valaes T, Tassapoulos N, Brinson AG (1965) Diverse characteristics of glucose-6-phosphate dehydrogenase from Greek children. J Lab Clin Med 65:212–221
Kirkman HN, Kidson C, Hennedy M (1968) Variants of human glucose-6-phosphate dehydrogenase. Studies of samples from New Guinea. In: Beutler E (ed) Hereditary disorders of erythrocyte metabolism. Grune and Stratton, New York, pp 126–146
Lisker R, Briceno RP, Zavala C, Navarette JI, Wessels M, Yoshida A (1977) A glucose-6-phosphate dehydrogenase Gd(-) Castilla variant characterized by mild deficiency associated with drug-induced hemolytic anemia. J Lab Clin Med 90:754–759
Luzzato L, Testa V (1978) Human erythrocyte glucose-6-phosphate dehydrogenase: structure and function in normal and mutant subjects. In: Pionelli, Jachnin (eds) Current topics in hematology, vol 1. New York
McCurdy P, Kamel K, Selim O (1974) Heterogeneity of red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency in Egypt. J Lab Clin Med 84:673–680
Pellicer A, Casado A (1970) Frequency of thalassemia and G6PD deficiency in five provinces of Spain. Am J Hum Genet 22:298–303
Rattazzi C (1969) Isolation and purification of human erythrocyte glucose 6-phosphate dehydrogenase from small amounts of blood. Biochim Biophys Acta 181:1–11
Rattazzi MC, Lenzerini L, Meera Khan P, Luzzato L (1969) Characterization of glucose-6-phosphate dehydrogenase: Variants II G6PD Kephalonia G6PD Attica and G6PD “Seattle-like” found in Greece. Am J Hum Genet 21:154–167
Sanrone G, Perroni L (1973) Variant-A delle G6PD in un familiare di origine siciliana. Pathologica 65:81–83
Stamatayannopoulos G, Yoshida A, Bacopoulos C, Motulsky AG (1967) Athens variant of glucose-6-phosphate dehydrogenase. Science 157:831–832
Stamatayannopoulos G, Voigtlander V, Kotsakis P, Akrivakis A (1971) Genetic diversity of the “Mediterranean” glucose 6-phosphate dehydrogenase deficiency phenotype. J Clin Invest 50:1253–1261
Vives Corrons JL, Carrera A, Triginer J, Kahn A, Rozman C (1974) Déficit congénito de glucosa-6-phosphate deshidrogenasa. Variante lenta encontrada en una familia espanola. Relación con la variante Seattle? Sangre 19:435–439
Yoshida A, Lin M (1973) Regulation of glucose-6-phosphate dehydrogenase activity in red blood cells from hemolytic and non-hemolytic variant subjects. Blood 41:877–891
Yoshida A, Beutler E (1978) Human glucose-6-phosphate dehydrogenase variants: a supplementary tabulation. Ann Hum Genet 41:347–355
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Corrons, J.L.V., Pujades, A. Heterogeneity of “Mediterranean type” glucose-6-phosphate dehydrogenase (G6PD) deficiency in Spain and description of two new variants associated with favism. Hum Genet 60, 216–221 (1982). https://doi.org/10.1007/BF00303006
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DOI: https://doi.org/10.1007/BF00303006