ERYTHROENZYMOPATHIES - A MODEL OF COORDIN ATED BIOCHEMISTRY AND MOLECULAR-BIOLOGY

Since the discovery of glucose 6-phosphate dehydrogenase and pyruvate kinase deficiencies, many other erythrocyte enzymes abnormalities have been found. Most enzyme deficiencies from the Embden-Meyerhof pathway , pentose-phosphate pathway and nucleotide metabolism result in hemoly tic anemias which can also be a consequence of adenosine deaminase hyp eractivity. Hemolysis is considered to result from either low ATP leve l or NADPH insufficient production. On the other hand, a marked decrea se of 2,3-diphosphoglycerate, by increasing the O-2-affinity of the re d cells, induces polycythemia. Polycythemia can also result from dipho sphoglycerate mutase deficiency and pyruvate kinase hyperactivity. In most erythroenzymopathies the genetic transmission is recessive autoso mal (sometimes dominant such as in adenosine deaminase and pyruvate ki nase hyperactivities and diphosphoglycerate mutase deficiency). Glucos e 6-phosphate dehy drogenase and phosphoglycerate kinase deficiencies are X-chromosome linked. For many years the diagnosis of these enzymat ic abnormalities has relied upon enzymatic assays because of the very low quantity of materials. The techniques of molecular biology can now be used and presently most of the red cell enzymes have been cloned. In addition, genetic mutations are continuously reported and prenatal diagnosis can be proposed in some cases.