Inherited glucosephosphate isomerase deficiency. A review of known variants and some aspects of the pathomechanism of the deficiency.

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.