CAUSAL MECHANISMS OF MULTIPLE ACQUIRED RED-CELL ENZYME DEFECTS IN A PATIENT WITH ACQUIRED DYSERYTHROPOIESIS

Abstract

A patient with an unclassified form of acquired dyserythropoiesis had multiple defects in erythrocyte enzyme activity, involving especially pyruvate kinase (PK), glucose phosphate isomerase (GPl) and phosphofructokinase (PFK). The PK activity defect was associated with a normal concentration of PK-related antigen, and the enzyme could be reactivated during the procedure of partial purification of the enzyme. The concentration of GPl-related antigen was as reduced as the GPl enzymatic activity, and the defect was not improved by any treatment (cross-incubation of red cells or treatment of the hemolysate by SH [sulfhydryl] reagents); the residual enzyme had a normal stability to heat. and a normal electrophoretic and electrofocusing pattern. The PFK activity defect was not improved either by cross-incubation of red cells or by treatment with SH reagents. Immunologic data with antimuscle and antileukocyte antisera seemed to indicate that the defect involved especially the muscle-type subunit of erythrocyte PFK. In agreement with this assumption was the fact that deficient PFK was markedly more inhibited by ATP than normal enzyme. Changes similar to those of deficient PFK herein studied were noted for PFK of unfractionated erythrocytes from premature newborns or of old erythrocytes from full-term infants. Each of the 3 enzyme defects detected in the patient apparently could be due to a different mechanism, involving post-translational changes, decreased synthesis and possible reversion of the genetic regulation mechanisms of the abnormal erythroid precursors toward a fetal type. The possible relationships between these various phenomena and the nature of a hypothetical common underlying cause are discussed.