Abstract
At least 13 cases from 10 different families with glucosephosphate isomerase (GPI) deficiency have been observed. Recently two additional cases of nonspherocytic hemolytic anemia with GPI deficiency in different families were investigated and one GPI variant without GPI deficiency was found in our laboratory. In the first patient, pedigree studies and starch-gel electrophoresis revealed that he was homozygous for a particular identical variant gene. There were two incidences of consanguineous marriages in his family. The propositus K. S. had 3 isozyme bands, one of which migrated faster toward the cathode than the normal main band in red cell, white cell, liver, spleen and muscle. His parents and other heterozygous family members had almost a half GPI activity of the normal and had four isozyme bands, one of which migrated between the normal main band and the propositus' main band. These findings were quite different from those of the previously reported cases. In the second patient, the proposita T. H. and heterozygous parents and a sister had the same electrophoretic migration with lower GPI activity. A thermostability test revealed that the proposita T. H. had thermolabile GPI. In pH-GPI activity relation, the proposita's curve was shifted to the acidic side. The family had consanguineous marriage and the parents' isozyme had the same migration as the normal. There seems to be no reports so far on the same GPI deficiency as this case. These two cases were completely pure homozygous whereas the previously reported cases were double heterozygous for two different GPI deficient variant genes. GPI of the propositus K. S. was designated as GPI “Narita” and that of the proposita T. H. as GPI “Matsumoto”.
In the third case, total GPI activity was within the normal limits. However, GPI isozyme was different from the normal, in that there were four isozyme bands, and the second and third bands migrated faster than the normal ones, and the first and fourth bands were stained less densely than the second and third bands.
This abnormal isozyme was very similar to Detter's PHI (GPI) 2-1. The third case seems to be heterozygous for a non-deficient GPI variant gene. Detter et al. postulated that GPI molecule may be composed as a dimer with two subunits. Our findings strongly support his hypothesis. Pedigree studies and kinetic study in the third case are currently in progress in our laboratory.
