Les hémoglobines normales et pathologiques

Hemoglobin is the major protein in red cells responsible for the transport of oxygen (O2) from lung toward tissues and coming back of carbonic gas (CO2) from tissues toward lung. Its oligomeric structure allows a fine regulation by O2 it-self (allosteric effect) and by pH and 2,3-diphosphoglycerate. Iron ion (Fe2+) in the heme molecule carried by globin chains constitutive of hemoglobin is responsible for O2 transport. Mutations in genes encoding globin chains can modify solubility, stability, affinity for O2, linkage of Fe2+ or its oxidative state, of hemoglobin. The most usual mutation is that responsible for sickle cell disease with the appearance of HbS with abnormal migration in electrophoresis. Other mutations lead to mutant proteins less soluble and with abnormal migration ; this group of diseases is called hemoglobinoses, or qualitative abnormalities of hemoglobin. Other types of mutations are characterized by quantitative abnormalities, called thalassemia, with the defect in the synthesis of the α-chain in α-thalassemia or the β-chain in β-thalassemia. The exploration of these qualitative or quantitative abnormalities needs separative methods based on the differences in electric charges, such as alkaline or acidic electrophoresis in a gel or a capillary, isoelectrofocusing and ion-exchange chromatography. Often it would be necessary to quantify the abnormal Hb, also HbF and HbA2 with blood counting showing the hemolytic anemia and molecular genetics for the identification of the mutation. Other more specialized analyses are reserved to reference centers.