Thalassemia syndromes

Thalassemia syndromes are very frequent in some parts of the world, especially Mediterranean and Asiatic countries. When the genetic defect underlying these syndromes is severe, iron overload becomes one the major clinical problems and can be life-threatening.

Pathogenesis of iron overload

The pathogenesis of iron overload in patients with thalassemia is multifactorial. Iron overload can develop as a consequence of increased iron absorption from the gastrointestinal tract, similar to that which occurs in persons with hemochromatosis or transfusion-dependent anemias. Under normal conditions, iron homeostasis is maintained by modulation of absorption of dietary iron (the only way iron enters the body). This, in turn, is regulated by a balance between iron needed for the erythron (more than three-fourths of total body iron) and for storage. Thus, all conditions characterized by increased erythropoiesis or by a reduction of iron stores are accompanied by enhanced iron absorption. Moreover, patients who have anemia with increased but ineffective erythropoiesis are at greater risk of developing severe iron overload than patients with hemolytic anemias with increased and effective erythropoiesis, e.g., patients with hereditary spherocytosis, who rarely develop iron overload. In the presence of severe anemia, intestinal hypoxia also appears to increase iron absorption.

Anemia is very mild in β-thalassemia heterozygotes and in persons with α-thalassemia in whom two or three alpha globin genes are functioning, and associated iron overload is rare. In these patients, inefficient erythropoiesis is relatively mild.