Pyruvate Kinase Greensboro . A Four - Generation Study of a High K 0

The proband with lifelong hemolytic anemia has a high phosphoenolypyruvate (PEP) erythrocyte pyruvate kinase (PK) variant substantially but incompletely normalized by the allosteric modifier fructose-i .6-diphosphate (F-i ,6-P2) with conversion of sigmoidal to hyperbolic kinetics. Heterozygotes in four generations express qualitatively identical but less severely abnormal kinetics and lack overt hemolysis. Kinetic abnormalities are closely mimicked by sulfhydryl modification of normal PK. Three distinct clinical and metabolic phenotypes characterize the proband and two sisters: variant PK and hemolytic anemia. variant PK without clinical manifestations or hemolysis. and complete normality. Their mother, whose red cell PK is entirely