Hereditary pyruvate kinase deficiency: role of the abnormal enzyme in red cell pathophysiology.

Two new mutant Pks, electrophoretically identical but kinetically slightly different, are reported. These two clinically innocuous PK variants, encountered in two non-related subjects, have combined in their daughter to give a fully expressed haemolytic anaemia. The functional abnormalities of the daughter's PK (increased K0.5 PEP, abnormal response to FDP, increased urea and guanidine-HCl stability, abnormal isoelectrofocusing 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 haemolysis. The hypothesis is put forward that the cause of haemolysis in PK deficiency may be associated with another defect located in the red cell membrane.