Hereditary Pyruvate Kinase Deficiency: Role of the Abnormal Enzyme in Red Cell Pathophysiology

Abstract

Two new mutant K pyruvate kinases [PKs] electrophoretically identical but kinetically slightly different, are reported. These 2 clinically innocuous PK variants, encountered in 2 non-related subjects, combined in their daughter to give a fully expressed hemolytic anemia. The functional abnormalities of the daughter''s PK (increased K0.5 PEP [phosphoenolpyruvate], abnormal response to FDP [fructose-1,6-diphosphate], increased urea and guanidine-HCl stability, abnormal isoelectric focusing and electrophoretic patterns) were like those of the parents but more pronounced, except for thermostability that was normal in the proband although markedly decreased in both parents. The family examined demonstrates that there is no relationship between in vitro properties of the variant and the severity of hemolysis. The cause of hemolysis in PK deficiency may be associated with another defect located in the red cell membrane.