Summary
In a 5-year-old Italian girl with severe congenital hemolytic anemia, red cell GPI deficiency was proven, and found to be due to a new variant, ‘GPI Roma.’ The parents are first cousins and have been proven to be heterozygous for this variant.
GPI Roma was slightly unstable to heat and exhibited a slightly increased Michaelis constant for fructose-6-phosphate. A single predominant fastmigrating GPI form existed in the patient's white blood cells, while the electrophoretic pattern in the red cells was composed, in addition to this ‘fast band’, of a major band migrating as normal GPI and of an additional slow band. It is shown that this phenomenon may be ascribed to postsynthetic events modifying the charge of the mutant enzyme.
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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)
Arnold, H., Blume, K. G., Engelhardt, R., Löhr, G. W.: 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 (1974a)
Arnold, H., Hoffmann, A., Blume, K. G., Engelhardt, R., Löhr, G. W.: Zur Frage gewebespezifischer Izoenzyme der Glucosephosphatisomerase des Menschen. Klin. Wochenschr. 52, 149–151 (1974b)
Baugham, M. A., Valentine, W. N., Paglia, D. E., Ways, P. O., Simon, E. R., Demarsh, Q. B.: Hereditary hemolytic anemia with glucose phosphate isomerase deficiency, a new enzyme defect of human erythrocytes. Blood 32, 236–249 (1968)
Charache, S., Fox, J., McCurdy, P., Kazazian, H., Winslow, R.: Postsynthetic deamidation of hemoglobin Providence (β82 Lys→Asn, Asp) and its effect on oxygen transport. J. Clin. Invest. 59, 652–658 (1977)
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)
Hanash, S. M., Winter, W. P., Rucknagel, D. L.: Synthesis of haemoglobin Wayne in erythroid cells. Nature 269, 717–719 (1977)
Kahn, A., Hakim, J., Cottreau, D., Boivin, P.: Gd(-) Matam, an African G6PD variant with enzyme deficiency. Biochemical and immunological properties in various hemopoïetic tissues. Clin. Chim. Acta 59, 183–190 (1975)
Kahn, A., Marie, J., Desbois, J. C., Boivin, P.: Favism in a Portuguese family due to a deficient G6PD variant of “Canton” or “Canton-like” type. Acta Haematol. 56, 58–64 (1976a)
Kahn, A., Vives-Corrons, J. L., Bertrand, O., Cottreau, D., Marie, J., Boivin, P.: Glucosephosphate 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., Van Biervliet, J. P. M., Vives-Corrons, J. L., Cottreau, D., Staal, G. E. J.: Genetic and molecular mechanisms of the congenital defects in glucose phosphate isomerase activity: studies of four families. Ped. Res. 11, 1123–1129 (1977)
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)
Nakashima, K., Miwa, S., Oda, S., Oda, E., Matsumoto, N., Fukumoto, Y., Yamada, T.: Electrophoretic and kinetic studies of glucose phosphate isomerase (GPI) in two different Japanese families with GPI deficiency. Am. J. Hum. Genet. 25, 294–301 (1973)
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)
Schröter, W., Tillmann, W.: Congenital nonspherocytic hemolytic anemia associated with glycosephosphate isomerase deficiency: variant Paderborn. Klin. Wochenschr. 55, 393–396 (1977)
Staal, G. E. J., Akkerman, J. W. N., Eggermont, E., Van Biervliet, J. P.: A new variant of glucosephosphate isomerase deficiency. GPI Kortrijk. Clin. Chim. Acta 78, 121–127 (1977)
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 study. Humangenetik 29, 291–297 (1975)
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With the technical assistance of R. Kernemp
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Isacchi, G., Cottreau, D., Mandelli, F. et al. ‘GPI Roma’, a new glucose phosphate isomerase deficient variant. Hum Genet 46, 219–226 (1979). https://doi.org/10.1007/BF00291924
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DOI: https://doi.org/10.1007/BF00291924