Bases moléculaires et physiopathologiques des maladies de l'hémoglobine

Among haemoglobin diseases, two types are particularly important to consider: the structural abnormalities and the synthesis deficiencies. In the first type, abnormal haemoglobin (Hb) may be silent or functionally altered. Because it causes sickle cell disease, HbS is the most significant. Synthesis deficiencies are encountered among the very heterogeneous group of thalassaemias. Haemoglobin diseases represent an important public health problem in endemic countries, and in other parts of the world because of immigration. The pathophysiological mechanisms differ. Sickle cell disease is mostly a rheological disease and, more than anaemia, vaso-occlusion is its major feature. Even though it results from a single mutation, it is very variable in its clinical presentation, from very severe cases early in life, to a well tolerated condition. Anaemia is the hallmark of thalassaemias. Multiple mutations are involved, but the severity of the disease is only partially related to the nature of the mutation. In the two types, modulating genes are involved. Recent insights have shown the involvement and the modulating role of the vascular endothelium, more particularly in the pathophysiology of vaso-occlusion in sickle cell disease. Other factors are progressively unveiled, that modify the evolution of thalassaemia.