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Quantitative variations of red-cell cytochrome b5 reductase (NADH-methemoglobin-reductase) in the Algerian population

Evidence for defective alleles


A striking proportion of Algerian subjects was reported among patients with congenital recessive methemoglobinemia due to cytochrome b5 reductase deficiency (Kaplan et al. 1979).

A population survery was carried out in red blood cells from 1000 algerian subjects. In 16 subjects, the cytochrome b5 reductase activity was diminished by 50%. Family studies indicated the presence of a defective allele with an overall gene frequency of 0.008. Immunologically cross-reacting material was found in red cells with low cytochrome b5 reductase activity. Leukocytes exhibited normal levels of enzyme in some families and low levels in others suggesting that at least two different deficient alleles at the DIA1 locus were present in the Algerian population. A higher prevalence of the deficient allele(s) was found in subjects of Kabyle origin.

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  1. Choury D, Kaplan JC (1980) Diaphorase P: A new fetal isozyme identified in human placenta. Biochim Biophys Acta 613:18–25

  2. Dreyfus JC (1972) Bases moléculaires des maladies enzymatiques génétiques. Biochimie 54:559–571

  3. Hegesh E, Calmanovici N, Avron M (1968) New method for determining ferrohemoglobin reductase (NADH-methemoglobin reductase) in erythrocytes. J Lab Clin Med 72:339–344

  4. Hopkinson DA, Corney G, Cook PJL, Robson EB, Harris H (1970) Genetically determined electrophoretic variants of human red-cell NADH-diaphorase. Ann Hum Genet 34:1–10

  5. Jaffé ER (1981) Methemoglobinemia. In: Clinics in Haematology, vol 10, no 1: 99–122

  6. Kaplan JC (1966) Méthode de measure rapide de méthémoglobine dans les globules rouges. Nouv Rev Fr Hematol 6:809–811

  7. Kaplan JC, Beutler E (1967) Electrophoretic red-cell NADH and NADPH diaphorases in normal subjects and patients with congenital methemoglobinemia. Biochem Biophys Res Commun 29: 606–610

  8. Kaplan JC, Leroux A, Bakouri S, Grangaud JP, Benabadji M (1974) La lésion enzymatique dans la méthémoglobinémie congénitale récessive avec encéphalopathie (Variante Béni-Messous). Nouv Rev Fr Hematol 173, no 6:755–770

  9. Kaplan JC, Leroux A, Beauvais P (1979) Formes cliniques du déficit en cytochrome b5 réductase. CR Soc Biol 173:368–379

  10. Leroux A, Junien C, Kaplan JC, Bamberger (1975) Generalized deficiency of cytochrome b5 reductase in congenital methemoglobinemia with mental retardation. Nature 258:619–620

  11. Leroux A, Torlinski L, Kaplan JC (1977) Soluble and microsomal forms of NADH-cytochrome b5 reductase of human placeta. Similarity with NADH-methemoglobin reductase from human erythrocytes. Biochim Biophys Acta 481:50–62

  12. Lostanlen D, Gacon G, Kaplan JC (1980) Direct enzyme titration curve of NADH-cytochrome b5 reductase by combined isoelectric focusing/electrophoresis. Eur J Biochem 112:179–183

  13. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

  14. Omura T, Takesue S (1970) A new method for simultaneous purification of cytochrome b5 and NADH-cytochrome reductase from rat liver microsomes. J Biochem (Tokyo) 67:249–257

  15. Righetti PG, Krishnamoorty R, Gianazza E, Labie D (1978) Protein titration curve by combined isoelectric focusing-electrophoresis with hemoglobin mutants as models. J Chromatogr 166:455–460

  16. Ross JD (1963) Deficient activity of DPNH-dependent methemoglobin diaphorase in cord blood erythrocytes. Blood 21:51–62

  17. Scott EM, McGraw JC (1962) Purification and properties of diphosphopyridine nucleotide diaphorase of human erythrocytes. J Biol Chem 237:249–222

  18. Zamudio I, Canessa M (1966) NADH-deshydrogenase activity of human erythrocyte membranes. Biochem Biophys Acta 120:105–109

  19. Zjilstra WG, Von Kampen EJ (1961) Standardization of the hemoglobinometry: the hemoglobin cyanid method. Clin Chim Acta 6: 538–541

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Correspondence to J. C. Kaplan.

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Reghis, A., Benabadji, M., Tchen, P. et al. Quantitative variations of red-cell cytochrome b5 reductase (NADH-methemoglobin-reductase) in the Algerian population. Hum Genet 59, 148–153 (1981).

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  • Internal Medicine
  • Blood Cell
  • Normal Level
  • Metabolic Disease
  • Quantitative Variation