Red cell enzyme anomalies

Abstract

SummaryRecent advances in the field of red cell enzyme anomalies are reviewed with a stress on G6PD as a genetic marker and on hereditary hemolytic anemia due to red cell enzyme anomalies. Using G6PD as a genetic marker, most benign and malignant tumors have been shown to have a clonal origin, except for neurofibroma and veneral warts which are clearly polyclonal. Recently, the primary structure of human red cell phosphoglycerate kinase was clarified and moreover, single amino acid substitutions of four mutant phosphoglycerate kinases were determined. To accomplish this, a method which requires only 20 ml of blood has been developed. It is a consensus among investigators in this field that the pathogenesis in three-quarters of the congenital nonspherocytic hemolytic anemia patients remain unknown even after adequate red cell enzyme studies which are now available, as well as Carrell's isopropanol test for the detection of unstable hemoglobins. IntroductionProgress in understanding red cell enzyme anomalies has been rapid in the last two decades owing to the fact that red cells are easy to obtain repeatedly from the patients and that enzymology has advanced a great deal. Since the discovery of glucose 6-phosphate dehydrogenase (G6PD) deficiency in 1956 and pyruvate kinase deficiency in 1961, 16 kinds of red cell enzyme anomalies associated with hereditary hemolytic anemia have been found so far. Moreover, it has become apparent that most, if not all, of the above-mentioned hemolytic anemias were caused by a functionally abnormal enzymes due to structural gene mutation. Single amino acid substitution was proven in a couple of G6PD variants and quite recently, in four mutant phosphoglycerate kinases. Complete amino acid sequence has been obtained in this particular enzyme recently. In this symposium, first I would like to make a brief review of the studies of G6PD as a genetic marker, followed by some recent topics of red cell enzyme anomalies mainly associated with hereditary hemolytic anemia.