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Erythrocyte pyruvate kinase deficiency: A kinetic method for differentiation between heterozygosity and compound‐heterozygosity
Author(s) -
Lakomek Max,
Winkler Heinz,
Linne Sabine,
Schröter Werner
Publication year - 1989
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830310402
Subject(s) - heterozygote advantage , pyruvate kinase , phosphoenolpyruvate carboxykinase , loss of heterozygosity , compound heterozygosity , enzyme , cooperativity , biology , reticulocytosis , biochemistry , chemistry , allele , medicine , glycolysis , gene , anemia
The goal of the present study was to search for criteria that allow one to distinguish between normal individuals and heterozygotes as well as compound heterozygotes for pyruvate kinase (PK) deficiency. As the residual activity of PK with heterozygotes was between 35% and 110% of the normal activity, it was necessary to find other methods to prove heterozygosity. The PK in the hemolysates of 23 patients suffering from PK deficiency, 36 paternal and maternal enzymes as well as the enzymes of five heterozygous and four normal siblings together with those of 20 normal individuals, were studied according to the recommendations of the International Committee for Standardization in Haematology. The following hematological and enzyme kinetic parameters can serve to identify heterozygotes for PK deficiency: 1) a slight reticulocytosis, 2) an up‐to‐twofold increase of the intracellular concentrations of glucose‐6‐phosphate in the erythrocyte, 3) a mixed cooperativity of the phosphoenolpyruvate (PEP)‐binding process of PK, 4) a decreased nucleotide specificity with guanosine diphosphate and uridine diphosphate, and 5) a lowered affinity for adenosine diphosphate. The most significant criterium found with all heterozygotes was a mixed cooperativity of the PEP‐binding process caused by the presence of a mixture of normal and mutant PK.