Summary
Two new deficient glucose-phosphate-isomerase (GPI) variants have been described in patients suffering from severe chronic hemolytic anemias. The patients' parents were consanguineous, such that the patients were true homozygotes for the mutated GPI genes. In both cases the main cause of the defect in enzyme activity was molecular instability of the mutated GPI molecules, their catalytic activity being nearly normal.
GPI ‘Paris’ was characterized by a slow electrophoretic migration and, above all, a drastically altered affinity for the substrates glucose-6-phosphate (decreased) and fructose-6-phosphate (increased). GPI “Enfants malades’ exhibited a slightly reduced electrophoretic mobility, an abnormal curve of the activity in function of pH, and an abnormal ratio of maximal velocity in the backward direction (fructose-6-phosphate»glucose-6-phosphate) to that in the forward direction (glucose-6-phosphate»fructose-6-phosphate).
No clear relation could be proved between the kinetic abnormalities of the mutant GPI variants on the one hand and the metabolic changes of the GPI-deficient red cells and the severity of hemolysis on the other.
Finally we emphasized the possible role of the impairment of hexosemonophosphate pathway in the reduction of viability of the GPI-deficient red cells.
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References
Arnold, H., Blume, K. G., Engelhardt, R., Löhr, G. W.: Glucosephosphate isomerase deficiency. Evidence for in vivo instability of an enzyme variant with hemolysis. Blood 41, 691–699 (1973a)
Arnold, H., Engelhardt, R., Löhr, G. W., Jacobi, H., Liebold, I.: Glucosephosphat-Isomerase Typ Recklinghausen: Eine neue Defektvariante mit hämolytischer Anämie. Klin. Wochenschr. 51, 1198–1204 (1973b)
Arnold, H., Hoffmann, A., Blume, K. G., Engelhardt, R., Löhr, G. W.: Zur Frage gewebespezifischer Isoenzyme der Glucosephosphatisomerase des Menschen. Klin. Wochenschr. 52, 149–151 (1974)
Baughan, M. A., Valentine, W. N., Paglia, D. E., Ways, P. O., Simon, E. R., Demarsh, Q. B.: Hereditary anemia associated with glucose phosphate isomerase deficiency. A new enzyme defect in human erythrocytes. Blood 30, 850 (1967)
Baughan, M. A., Valentine, W. N., Paglia, D. E., Ways, P. O., Simon, E. R., Demarsh, Q. B.: Hereditary hemolytic anemia with glucose phosphate isomerase (GPI) deficiency, a new enzyme defect of human erythrocytes. Blood 32, 236–249 (1968)
Bertrand, O., Kahn, A., Cottreau, D., Boivin, P.: Human leukocyte glucose phosphate isomerase. Purification by affinity elution and immunological study. Biochimie 58, 261–276 (1976)
Beutler, E.: Red cell metabolism, a manual of biochemical methods. New York, London: Grune and Stratton 1971
Beutler, E., Sigalove, W. H., Angusmuir, W., Matsumoto, F., West, C.: Glucosephosphate (GPI) deficiency: GPI elyria. Ann. Intern. Med. 80, 730–732 (1974)
Biervliet, J. P. G. M. Van: Glucosephosphate isomerase deficiency in a Dutch family. Acta Paediatr. Scand. 64, 868–972 (1975)
Biervliet, J. P. G. M. Van, Milligen-Boersma, L. Van, Staal, G. E. J.: A new variant of glucose phosphate isomerase deficiency (GPI Utrecht). Clin. Chim. Acta 65, 157–165 (1975)
Cartier, P., Leroux, J. P., Temkine, H.: Techniques de dosage des intermédiaires de la glycolyse dans les tissus. Ann. Biol. Clin. 25, 791–813 (1967a)
Cartier, P., Temkine, H.: Le 2–3 diphosphoglycerate et le glucose 1–6 diphosphate du globule rouge: techniques de dosage. Ann. Biol. Clin. 25, 1119–1128 (1967b)
Detter, J. C., Ways, P. O., Giblett, E. R., Hopkinson, D. A., Povey, S., Harris, H.: Inherited variations in human phosphohexose isomerase. Ann. Hum. Genet. 31, 329–338 (1968)
Harrison, R. A. P.: The detection of hexokinase, glucose phosphate isomerase and phosphoglucomutase activities in polyacrylamide gels after electrophoresis. A novel method using immobilized glucose 6 phosphate dehydrogenase. Anal. Biochem. 61, 500–507 (1974)
Kahana, S. E., Lowry, O. H., Schulz, D. W., Passoneau, J. V., Cranford, E. J.: The kinetics of phosphoglucose isomerase. J. Biol. Chem. 235, 2178–2184 (1960)
Kahn, A., Cottreau, D., Boyer, C., Marie, J., Galand, C., Boivin, P.: Causal mechanisms of multiple acquired red cell enzyme defects in a patient with acquired dyserythropoiesis. Blood 48, 653–662 (1976a)
Kahn, A., Vives-Corron, J. C., Bertrand, O., Cottreau, D., Marie, J., Boivin, P.: Glucose phosphate isomerase deficiency due to a new variant (GPI Barcelona) and to a silent gene. Biochemical, immunological and genetic studies. Clin. Chim. Acta 66, 145–155 (1976b)
Kahn, A., Biervliet, J. P. M. Van, Vives-Corrons, J. L., Cottreau, D., Staal, G. E. J.: Genetic and molecular mechanisms of the congenital defects in glucosephosphate isomerase activity. Studies of four families. Pediatr. Res. 11, 1123–1129 (1977)
Levine, L., Vunakis, H. Van: Micro complement fixation. Methods Enzymol 11, 928–936 (1967)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275 (1951)
McMorris, F. A., Chen, T. R., Ricciuti, F., Tischfield, J., Creagan, R., Ruddle, F.: Chromosome assignments in man of the genes for two hexosephosphate isomerases. Science 179, 1129–1131 (1973)
Miwa, S., Nakashima, K., Tajiri, M., Ono, J., Abe, S., Oda, E., Nonaka, H., Matsuoka, I., Shimoyama, S., Hirata, Y., Amaki, I., Yamaguchi, H., Nishina, T.: Three cases in two families with congenital non spherocytic hemolytic anemia due to defective glucosephosphate isomerase: GPI Matsumoto. Acta Haematol Jpn. 38, 238–247 (1975)
Müller, E., Marti, H. R., Bach, J. L., Gasser, C.: Hereditäre nicht sphärozytäre hämolytische Anämie durch Glukosephosphatisomerase-Mangel: der erste in der Schweiz beobachtete Fall. Schweiz. Med. Wochenschr. 104, 1379–1382 (1974)
Oski, F., Fuller, E.: Glucose-phosphate isomerase deficiency associated with abnormal osmotic fragility and spherocytes. Clin. Res. 19, 427 (1971)
Ouchterlony, O.: Diffusion in gel Methods for immunological analysis. Progr. Allergy 5, 1 (1958)
Paglia, D. E., Valentine, W. N.: Hereditary glucose phosphate isomerase deficiency. A review. Am. J. Clin. Pathol. 62, 740–751 (1974)
Paglia, D. E., Paredes, R., Valentine, W. N., Dorantes, S., Konrad, P. N.: Unique phenotypic expression of glucose-phosphate isomerase deficiency. Am. J. Hum. Genet. 27, 62–70 (1975)
Payne, D. M., Porter, D. W., Gracy, R. W.: Evidence against the occurrence of tissue specific variants and isoenzymes of phosphoglucose isomerase. Arch. Biochem. Biophys. 151, 122–127 (1972)
Ruddle, F. H.: Linkage analysis in man by somatic cell hybrids. Nature 242, 165–169 (1973)
Vives-Corrons, J. L., Rozman, C., Kahn, A., Carrera, A., Triginer, J.: Glucose phosphate isomerase deficiency with hereditary hemolytic anemia in a Spanish family: Clinical and familial studies. Hum. Genet. 29, 291–297 (1975)
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Kahn, A., Buc, HA., Girot, R. et al. Molecular and functional anomalies in two new mutant glucose-phosphate-isomerase variants with enzyme deficiency and chronic hemolysis. Hum Genet 40, 293–304 (1978). https://doi.org/10.1007/BF00272190
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DOI: https://doi.org/10.1007/BF00272190