For its frequency and severity β-thalassemia represents a significant health problem in various areas of the world. Progressive iron overload is a common complication of hemoglobinopathies and represents a major cause of morbidity and premature mortality in patients with β-thalassemia.The discovery of hepcidin and its role in iron homeostasis has revolutionized our understanding of the pathogenesis of iron overload and iron-restricted anemias, stimulating the development of new diagnostic and therapeutic modalities for these disorders. However, little is known about the relationship among ineffective erythropoiesis, the role of iron-regulatory genes, and tissue iron distribution in β-thalassemia. The chapter describes evidences for these relationships and discusses how recent discoveries on iron metabolism and erythropoiesis could lead to new therapeutic approaches and better clinical care of these diseases.
Part of the book: Inherited Hemoglobin Disorders
In β-thalassemia, the erythropoietic process is markedly altered, and the lack or reduced synthesis of β-globin chains induces an excess of free α-globin chains within the erythroid cells. Aggregation, denaturation, and degradation of these chains lead to the formation of insoluble precipitates causing damage to the red blood cell membrane. One of the major consequences in this genetic disorder is iron overload due to ineffective erythropoiesis and premature hemolysis in the plasma and in major organs such as heart, liver, and endocrine glands. The chapter describes the etiology of iron accumulation, the role of hepcidin in regulating increased iron absorption, and the pathophysiology resulting from excess of “free iron” and discusses new ways to decrease the iron overload and to neutralize its deleterious effects in the tissues other than iron chelation.
Part of the book: Beta Thalassemia