Recent progress in the molecular genetic analysis of erythroenzymopathy.

During the relatively recent period in which normal genes for most red cell enzymes have been isolated, the techniques of molecular biology have been applied to the studies of erythroenzymopathy. Single nucleotide substitutions have been identified in aldolase, triosephosphate isomerase, glucose 6-phosphate dehydrogenase, and adenylate kinase variants by the cloning and nucleotide sequence of the patients' genes. Up to now, all of the enzyme-deficient variants which have been investigated have been 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 transcriptional or translational efficiency.