Erythroenzymopathies : modèle d'études coordonnées par biochimie et biologie moléculaire.

Abstract

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 hemolytic anemias which can also be a consequence of adenosine deaminase hyperactivity. Hemolysis is considered to result from either low ATP level or NADPH insufficient production. On the other hand, a marked decrease of 2,3-diphosphoglycerate, by increasing the O-2-affinity of the red cells, induces polycythemia. Polycythemia can also result from diphosphoglycerate mutase deficiency and pyruvate kinase hyperactivity. In most erythroenzymopathies the genetic transmission is recessive autosomal (sometimes dominant such as in adenosine deaminase and pyruvate kinase hyperactivities and diphosphoglycerate mutase deficiency). Glucose 6-phosphate dehy drogenase and phosphoglycerate kinase deficiencies are X- chromosome linked. For many years the diagnosis of these enzymatic 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.