Hereditary Hemoglobinopathies

Haemoglobinopathies are a group of inherited disorders characterized by structural variations of the hemoglobin molecule. For survival, most of the patients require chronic red blood cells transfusions in order to overcome ineffective erythropoiesis. Unfortunately, all chronically transfused patients become clinically iron overloaded, as there is no physiological mechanism for the removal of iron from the body. The pathologic changes and clinical manifestations associated to chronic iron overload are common among all transfusional ironoverload patients, albeit best documented in patients with β-thalassemia major.

Thalassaemia is among the most common genetic disorders worldwide. It is widespread throughout the Mediterranean Region, Africa, Middle East, the Indian subcontinent and Burma, southeast Asia, including southern China, the Malay Peninsula, and Indonesia.

β-thalassaemia major represents the majority of thalassaemia cases that are clinically relevant. While reliable sources estimate that about 1.5% of the global population – 80 million/90 million people – are carriers of β-thalassaemia, with about 60,000 affected children born annually (the great majority in the developing world), it is certain that these figures are a gross underestimation. According to TIF records, about 200,000 patients are alive and registered as receiving treatment around the world, underlining the bitter reality that the majority of affected children, born in developing countries, die undiagnosed or misdiagnosed, receive sub-optimal treatment or are left untreated altogether.

Frequent transfusions are the recommended treatment for β-thalassemic patients in order to suppress ineffective erythropoiesis and to provide adequate oxygen carrying capacity. However, in the most severe forms of transfusion-dependent anemia, after only a few years on regular transfusion regimen, the iron storage capacity of the liver and other organs is exceeded, thus leading, in absence of an adequate intervention, to the development of a multi-system organ dysfunction which, in most cases, is lethal. Consequently an iron chelation therapy is necessary for the removal of excess iron.