Congenital nonspherocyte hemolytic anemia due to functionally abnormal pyruvate kinase. Report of a case.

Abstract

Six-years-old Japanese girl (N.O.) with congenital nonspherocytic hemolytic anemia was presented. Her parents are first cousins. Although erythrocyte pyruvate kinase (PK) showed above normal activity under usual assay conditions in this case, analysis of red cell glycolytic intermediates pointed a disturbance in glycolysis at the PK step, showing Oigh phosphoenolpyruvate, 2-phosphoglycerate, 3-phosphoglycerate as well as 2, 3-diphosphoglycerate concentrations and low ATP level. Further studies on partially purified erythrocyte PK from the patient revealed marked elevation of Michaelis constant for phosphoenolpyruvate and change in optimum pH as compared to that of normal subject.
It is most likely that there are at least several variants of PK as in case of glucose 6-phosphate dehydrogenase, and that the present case come under one of unusual PK variants. In this particular case, hemolytic anemia is probably caused by a production of an abnormal enzyme protein rather than decreased synthesis of normal PK.