Erythrocyte pyruvate kinase deficiency: relations of residual enzyme activity, altered regulation of defective enzymes and concentrations of high-energy phosphates with the severity of clinical manifestation.

Abstract

The defective enzymes of 54 patients with pyruvate kinase (PK) deficiency were characterized according to the recommendations of the International Committee for Standardization in Haematology (ICSH). The erythrocyte PK activity in whole blood was calculated considering the 16-fold higher activity of the reticulocyte enzyme (AR) compared to the erythrocyte enzyme (AE). The following parameters turned out to give a good correlation to the degree of haemolytic anaemia and can therefore serve as a prognostic tool: All patients with a severe course of the disease had residual erythrocyte PK activities less than 33% of the normal enzymes (percentage activity), and patients with mild haemolytic anaemia exhibited residual activity values below and above this threshold value. Studies of enzyme cooperative showed that positive cooperative or mixed cooperative phosphoenolpyruvate (PEP) binding with a predominant positive cooperative part appeared in all cases with a mild clinical course, and about one-third of the severe ones. Negative cooperativity or mixed cooperativity with predominant negative cooperative part was observed only with severe haemolytic anaemia. Furthermore, the determination of glucose-6-phosphate (G-6-P) turned out to be a good prognostic criterion, i.e. all patients with mild clinical course exhibited G-6-P-concentrations lower than 0.11 mumol/l red blood cells. In the case of patients with severe haemolytic anaemia, about 80% showed values higher than 0.11 mumol/l RBC.