Glucosephosphate Isomerase Deficiency: Evidence for In Vivo Instability of an Enzyme Variant With Hemolysis

Pathogenesis of hemolysis in glucose-phosphate isomerase (GPI) deficiency was studied. Red cell populations of different ages were obtained by density centrifugation. In comparison to cell populations with comparable amount of reticulocytes, GPI activity decreased faster in the deficient red cells. A method to simulate aging blood cells in vitro was devised. On the first day the rate of glycolysis was normal in the deficient cells, but by the eighth day of the incubation period, the metabolic capacity decreased markedly, and hemolysis was observed. Using mannose as a source of energy, the rate of glycolysis was still normal by the eighth day, which reflects the cause and effect relationship between impairment of energy metabolism and GPI deficiency. It may be concluded that hemolytic anemia in this case of GPI deficiency is caused by the synthesis of a qualitatively changed subunit of the GPI molecule, which is associated with faster inactivation of the enzyme in vivo.