Red cell glucosephosphate isomerase deficiency: Two new mutant enzymes

Two cases of congenital non spherocytic haemolytic anaemia associated with new glucosephosphate isomerase (GPI) variants are reported. The defective enzyme from one patient showed increased affinity for fructose-6-phosphate (F-6-P), decreased affinity for glucose-6-phosphate (G-6-P), altered electrophoretic and isoelectrofocusing patterns and shift to the left of the precipitin curve; the enzyme was stable under all the conditions tested. The GPI variant from the other patient displayed a marked instability to heat, urea and guanidine-HCI, the other biochemical and immunological characteristics being normal; this mutant enzyme was associated in the red cells with deficiency and instability of reduced glutathione (GSH) and altered carbohydrate membrane composition. Family studies suggest that the first patient is homozygous while the second is doubly heterozygous for a maternal gene producing an inactive enzyme and a paternal gene responsible for a structural alteration resulting in marked enzyme lability.