Skip to main content
SpringerLink
Log in

Inherited glucosephosphate isomerase deficiency

A review of known variants and some aspects of the pathomechanism of the deficiency

HereditÄrer Glukosephosphat-Isomerase-Mangel

Bekannte Varianten und einige Aspekte seines Pathomechanismus

  • Review Article
  • Published:
Blut Aims and scope Submit manuscript

Zusammenfassung

Seit der Erstbeschreibung des GPI-Mangels 1967 wurden zahlreiche Patienten aus allen Teilen der Welt mitgeteilt. Die Patienten leiden an einer typischen nicht-sphÄrozytÄren hÄmolytischen AnÄmie mit krisenhafter Verschlechterung wÄhrend akuter Infektionen. Die Erkrankung wird autosomal rezessiv vererbt, die HÄlfte der Patienten ist homozygot, die anderen doppelt-heterozygot.

Die biochemischen Eigenschaften der defekten Enzyme variieren stark, so da\ verschiedene Varianten beschrieben wurden. Die physiko-chemischen Eigenschaften sind hÄufiger verÄndert als die kinetischen. Alle Defekt-Varianten sind mehr oder weniger instabil. Die wÄhrend der Zellalterung fortschreitende Verminderung der GPI-AktivitÄt führt zu einem Anstieg des G6P, und bei in vitro gealterten Erythrozyten zu einem dramatischen Abfall der Glycolyserate und gleichzeitiger HÄmolyse der Zellen. Die Ursache der GlycolyseeinschrÄnkung scheint die Verminderung der GPI-AktivitÄt selbst und nicht etwa eine Hemmung der Hexokinase durch das erhöhte G6P zu sein.

Summary

Since the first report of GPI deficiency in 1967 many patients from all over the world have been described. The patients suffer from a typical nonspherocytic hemolytic anemia with hemolytic crises during acute infections. The disease is inherited as an autosomal recessive, half of the patients are homozygotic, the others are double heterozygotes. The biochemical properties of the deficient enzymes vary widely. Thus, many well characterized enzymes have been designated as different variants. The modification of physicochemical properties surpasses kinetic aberrations. All defective variants are more or less unstable.

The activity diminishes progressively, leading to a rise in G6P concentration and in red cells after aging in vitro to a dramatic impairment of glycolysis and concomittant hemolysis. The cause of the metabolic block is the diminished GPI activity itself and not an inhibition of hexokinase by the high G6P.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Arnold, H., Blume, K.G., Busch, D., Lenkeit, U., Löhr, G.W., Lübs, E.: Klinische und biochemische Untersuchungen zur Glucosephosphatisomerase normaler menschlicher Erythrozyten und bei Glucosephosphatisomerase-Mangel. Klin. Wochenschr.48, 1299–1308 (1970)

    Google Scholar 

  2. Arnold, H., Blume, K.G., Engelhardt, R., Löhr, G.W.: Glucose-phosphate isomerase deficiency: Evidence for in vivo instability of an enzyme variant with hemolysis. Blood41, 691–699 (1973)

    Google Scholar 

  3. Arnold, H., Engelhardt, R., Löhr, G.W., Jacobi, H., Liebold, L: Glucosephosphat-Isomerase Typ Recklinghausen: Eine neue Defektvariante mit hÄmolytischer AnÄmie. Klin. Wochenschr.51, 1198–1204 (1973)

    Google Scholar 

  4. Arnold, H., Blume, K.G., Engelhardt, R., Löhr, G.W.: Zum Mechanismus der Glycolysehemmung von Erythrozyten mit Glucosephosphat-Isomerase-Defekt. Abhandl. Akad. Wissensch. DDR., Jhrg. 1973, 355–358

  5. 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)

    Google Scholar 

  6. Arnold, H., Blume, K.G., Schröter, W., Löhr, G.W., Koch, H.H., Wonneberger, B.: Glucose phosphate isomerase deficiency with congenital nonspherocytic hemolytic anemia: A new variant (type Nordhorn). II. Purification and biochemical properties of the defective enzyme. Pediatr. Res.8, 26–30 (1974)

    Google Scholar 

  7. Arnold, H., Blume, K.G., Löhr, G.W., Boulard, M., Najean, Y.: “Acquired” red cell enzyme defects in hematological diseases. Clin. Chim. Acta57, 187–189 (1974)

    Google Scholar 

  8. Arnold, H., Seiberling, M., Blume, K.G., Löhr, G.W.: Immunological studies on glucosephosphate isomerase deficiency: Instability and impaired synthesis of the defective enzyme. Klin. Wochenschr.53, 1135–1136 (1975)

    Google Scholar 

  9. Arnold, H., Dodinval-Versie, J., Lambotte, C., Löhr, G.W., van der Hofstadt, J.: Glucosephospatisomerase deficiency type Liege: A new variant with congenital nonspherocytic hemolytic anemia. Blut35, 187–193 (1977)

    Google Scholar 

  10. Baughan, M.A., Valentine, W.N., Paglia, D.E., Ways, P.O., Simon, E.R., De Marsh, Q.B.: Hereditary hemolytic anemia associated with glucosephosphate isomerase (GPI) deficiency: A new enzyme defect of human erythrocytes. Blood30, 850 (1967)

    Google Scholar 

  11. Baughan, M. A., Valentine, W.N., Paglia, D.E., Ways, P.O., Simon, E.R., De Marsh, Q.B.: Hereditary hemolytic anemia associated with glucosephosphate isomerase (GPI) deficiency — a new enzyme defect of human erythrocytes. Blood32, 236–249 (1968)

    Google Scholar 

  12. Bello, A., Pricher, H., Dorantes, S.: Personal communication 1973, quoted after Paglia, D. and Valentine, W.N. Am. J. Clin. Pathol.62, 740–751 (1974)

    Google Scholar 

  13. Beutler, E., Sigalove, W.H., Angusmuir, W., Matsumoto, F., West, C.: Glucosephosphate isomerase (GPI) deficiency: GPI elyria. Ann. Intern. Med.80, 730–732 (1974)

    Google Scholar 

  14. Blume, K.G., Hryniuk, W., Powars, D., Trinidad, F., West, C., Beutler, E.: Characterization of new variant of glucosephosphate-isomerase deficiency with hereditary nonspherocytic hemolytic anemia. J. Lab. Clin. Med.97, 942–949 (1972)

    Google Scholar 

  15. Blackburn, M.N., Chirgwin, J.M., James, G.T., Kempe, T.D., Parsons, T.F., Register, A.M., Schnackerz, K.D., Noltmann, E.A.: Pseudoisoenzymes of rabbit muscle phosphoglucose isomerase. J. Biol. Chem.247, 1170–1179 (1972)

    Google Scholar 

  16. Boivin, P., Galand, C., Hakim, J., Kahn, A.: Acquired erythroenzymaties in blood disorders: Study of 200 cases. Br. J. Haematol.31, 531–543 (1975)

    Google Scholar 

  17. Cartier, P., Temkine, H., Griscelli, C.: Etude biochimique d'une anemie hemolytique avec dedicit familial en phosphohexisomerase. Enzymol. Biol. Clin.10, 439 (1969)

    Google Scholar 

  18. Cayanis, E., Penfold, O.K., Freiman, I., MacDougall, L.G.: Haemolytic anaemia associated with glucosephosphate isomerase (GPI) deficiency in black South African child. Br. J. Haematol.37, 363–371 (1977)

    Google Scholar 

  19. Detter, J.C., Ways, P.O., Giblett, E.R., Baughan, M.A., Hopkinson, D.A., Povey, S., Harris, H.: Inherited variations in human phosphohexose isomerase. Ann. Hum. Genet.31, 329–338 (1968)

    Google Scholar 

  20. Gilsanz, F., Barbolla, L., Fernandez, M.N.: Congenital nonspherocytic hemolytic anemia due to glucosephosphate isomerase deficiency. III. Congr. Europ. Div. of Intern. Soc. Hematol., London, Abstr. No. 30, 20, 1975

    Google Scholar 

  21. Helleman, P.W., Van Biervliet, J.P.G.M.: Hematological studies in a new variant of glucosephosphate isomerase deficiency (GPI Utrecht). Helv. Paediatr. Acta30, 525–536 (1975)

    Google Scholar 

  22. Hutton, J.J., Chilcote, R.R.: Glucose phosphate isomerase deficiency with hereditary nonspherocytic hemolytic anemia. J. Pediatr.85, 494–497 (1974)

    Google Scholar 

  23. 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)

    Google Scholar 

  24. Kahn, A., Cottreau, D., Boyer, C., Marie, J., Galand, O., Boivin, P.: Causal mechanisms of multiple acquired red cell enzyme defects in a patient with acquired dyserythropoesis. Blood48, 653–662 (1976)

    Google Scholar 

  25. 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. Acta66, 145–155 (1976)

    Google Scholar 

  26. 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)

    Google Scholar 

  27. Kahn, A., Buc, H.A., Girot, R., Cottreau, D., Griscelli, C.: Molecular and functional anomalies in two new mutant glucose-phosphate-isomerase variants with enzyme deficiency and chronic hemolysis. Hum. Genet.40, 293–304 (1978)

    Google Scholar 

  28. Leger, J., Bost, M., Kolodie, L., Schaerer, R., Hollard, D.: Anemie hemolytique congenitale et familia avec deficit en phospho-hexose-isomerase (PHI) et elliptocytose. 13. Congr. Intern. Soc. Hematol., München, Abstr. Vol. 293, 1970

  29. Löhr, G.W., Arnold, H., Blume, K.G., Engelhardt, R., Beutler, E.: Hereditary deficiency of glucosephosphate isomerase as a cause of nonspherocytic hemolytic anemia. Blut26, 393–398 (1973)

    Google Scholar 

  30. Lovric, V.A.: Personal communication 1974

  31. Matsumoto, N., Ishihara, T., Oda, E., Miwa, S., Nakashima, K., Uchino, F., Fukumoto, Y.: Fine structure of the splen and liver in glucosephosphate isomerase (GPI) deficiency hereditary nonspherocytic hemolytic anemia — Selective reticulocyte destruction as a mechanism of hemolysis. Acta Haematol. Jpn.36, 46–54 (1973)

    Google Scholar 

  32. Miwa, S., Nakashima, K., Oda, S., Oda, E., Matsumoto, N., Ogawa, S., Fukumoto, Y.: Glucosephosphate isomerase (GPI) deficiency hereditary nonspherocytic hemolytic anemia. Report of the first case found in Japanese. Acta Haematol. Jpn.36, 65–69 (1973)

    Google Scholar 

  33. Miwa, S., Nakashima, K., Oda, S., Matsumoto, N., Ogawa, H., Kobayashi, R., Kotani, M., Harata, A., Onaya, T., Yamada, T.: Glucosephosphate isomerase (GPI) deficiency hereditary nonspherocytic hemolytic anemia. Report of the second case found in Japanese. Acta Haemat. Jpn.36, 70–73 (1973)

    Google Scholar 

  34. Miwa, S., Nakashima, K., Tajiri, M., Ono, J., Abe, S., Oda, E., Nonaka, H., Matsuoka, I., Shimoyama, S., Hirata, Y., Amaki, I., Horiuchi, A., 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)

    Google Scholar 

  35. Müller, E., Marti, H.R., Bach, J., Micheli, 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)

    Google Scholar 

  36. Nakashima, K., Miwa, S., Oda, S., Oda, E., Matsumoto, N., Fukumoto, Y., Yamada, T.: Elektrophoretic and kinetic studies of glucosephosphate isomerase (GPI) in two different Japanese families with GPI deficiency. Am. J. Hum. Genet.25, 294–301 (1973)

    Google Scholar 

  37. Oski, F., Fuller, E.: Glucose-phosphate isomerase (GPI) associated with abnormal osmotic fragility and spherocytes. Clin. Res.19, 427 (1971)

    Google Scholar 

  38. Paglia, D. E., Holland, P., Baughan, M.A., Valentine, W.N.: Occurrence of defective hexosephosphate isomerization in human erythrocytes and leukocytes. N. Engl. J. Med.280, 66–71 (1969)

    Google Scholar 

  39. Paglia, D.E., Valentine, W.N.: Hereditary glucose-phosphate isomerase deficiency. A review. Am. J. Clin. Pathol.62, 740–751 (1974)

    Google Scholar 

  40. Paglia, D.E., Paredes, R., Valentine, W.N., Dorantes, S., Konrad, P.N.: Unique phenotypic expression of glucosephosphate isomerase deficiency. Am. J. Hum. Genet.27, 62–70 (1970)

    Google Scholar 

  41. 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)

    Google Scholar 

  42. Rotteveel, J.J., de Vaan, G.A.M., Staal, G.E.J., Van Biervliet, J.P.G.M., Schretlen, E.D.A.M.: Glucosephosphate isomerase deficiency, a new variant in a Dutchfamiliy. Case report. Eur. J. Pediatr.125, 21–28 (1977)

    Google Scholar 

  43. Schroeder, M., Foerster, J., Beutler, E.: Pers. commun. 1971, quoted after Paglia D. and Valentine, W.N. Am. J. Clin. Pathol.62, 740–751 (1974)

    Google Scholar 

  44. Schröter, W., Brittinger, G., Zimmerschitt, E., König, E., Schrader, D.: Combined glucosephosphate isomerase and glucose-6-phosphate dehydrogenase deficiency of the erythrocytes: A new hemolytic syndrome. Br. J. Haematol.20, 249–261 (1971)

    Google Scholar 

  45. Schröter, W., Koch, H.H., Wonneberger, B., Kalinowsky, W., Arnold, A., Blume, K.G., Hüther, W.: Glucosephosphate isomerase deficiency with congenital nonspherocytic hemolytic anemia. A new variant (type Nordhorn). I. Clinical and genetic studies. Pediatr. Res.8, 18–25 (1974)

    Google Scholar 

  46. Schröter, W., Tillmann, W., Congenital nonspherocytic hemolyticanem ia associated with glucosephosphate isomerase deficiency: Variant Paderborn. Klin. Wochenschr.55, 393–396 (1977)

    Google Scholar 

  47. Slein, M.W.: Phosphohexoseisomerase from muscle. In: Methods in enzymology. Vol. I., p. 299, New York: Academic Press 1955

    Google Scholar 

  48. Staal, G.E.J., Akkerman, J.W.N., Eggermont, E., Van Biervliet, J.P.G.M.: A new variant of glucosephosphate isomerase deficiency: GPI-Kortrijk. Clin. Chim. Acta78, 121–127 (1977)

    Google Scholar 

  49. Tariverdian, G., Arnold, H., Blume, K.G., Lenkeit, U., Löhr, G.W.: Zur Formalgenetik der Phosphoglucose-isomerase (EC: 5.3.1.9.): Untersuchung einer Sippe mit GPI-Defizienz. Humangenetik10, 218–223 (1970)

    Google Scholar 

  50. Tilley, B.W., Gracy, R.W., Welch, S.G.: A point mutation increasing the stability of human phosphoglucose isomerase. J. Biol. Chem.249, 4571–4579 (1974)

    Google Scholar 

  51. Van Biervliet, J.P.G.M., Van Milligen-Boersma, L., Stall, G. E. J.: A new variant of glucosephosphate isomerase deficiency (GPI-Utrecht). Clin. Chim. Acta65, 157–165 (1975)

    Google Scholar 

  52. Van Biervliet, J.P.G.M.: Glucosephosphate isomerase deficiency in a Dutch family. Acta Paediatr. Scand.64, 868–872 (1975)

    Google Scholar 

  53. Van Biervliet, J.P.G.H., Vlug, A., Bartstra, H., Rotteveel, J. J., DeVan, G. A.M., Staal, G.E.J.: A new variant of glucosephosphate isomerase deficiency. Humangenetik30, 35 (1975)

    Google Scholar 

  54. Vives-Corrons, J.L., Rozman, C., Kahn, A., Triginer, J.: Glucose phosphate isomerase deficiency with hereditary hemolytic anemia in a Spanish family: Clinical and familial studies. Humangenetik29, 291–297 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medizinische UniversitÄtsklinik, Hugstetterstra\e 55, D-7800, Freiburg i. Br., Germany

    H. Arnold

Authors
  1. H. Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arnold, H. Inherited glucosephosphate isomerase deficiency. Blut 39, 405–417 (1979). https://doi.org/10.1007/BF01008661

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01008661

Schlüsselwörter

Key words

Search

Navigation