[Pathophysiology and laboratory tests of hemolytic anemia: with special reference to erythroenzymopathies].

Since the discovery of glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase deficiency, erythroenzymopathies associated with hereditary hemolytic anemia have been extensively investigated. Kinetic and electrophoretic studies have shown that most erythroenzymopathies are caused by the production of a mutant enzyme. Single amino acid substitutions have been determined in G6PD and phosphoglycerate kinase variants by studies of the enzyme. Except for these two enzymes, it has been difficult to purify and to characterize the patient's enzyme because of the low protein contents in red blood cells. Recent advance in recombinant DNA technology has made possible the isolation of normal genomic DNA or cDNA for several enzymes. These results permit us to study the molecular basis of erythroenzymopathies at the nucleotide level. Single base substitutions have been identified in aldolase, triosephosphate isomerase, G6PD and adenylate kinase variants by the cloning and nucleotide sequence of the patients' genes. To date, all of the enzyme-deficient variants which have been investigated are caused by point mutations. An exception is a hemolytic anemia secondary to increased adenosine deaminase (ADA) activity. Red cell ADA activity increases on the order of a hundred-fold in affected individuals. The basic abnormality appears to result from overproduction of structurally normal enzyme due to abnormal translational efficiency.