21 - Iron overload associated with thalassemia syndromes

Summary

Introduction

Thalassemia comprises a diverse group of heritable disorders that decrease the synthesis of one or more globin chains. Specific thalassemia syndromes are named by the affected globin chain(s) or the causative mutation(s). Thalassemia is prevalent in some areas of the world, especially those in which malaria is or was endemic such as the Mediterranean region or southeast Asia. Many thalassemia mutations cause anemia, the severity of which varies with thalassemia or co-inherited hemoglobinopathy genotype, and the consequent effect on globin and hemoglobin synthesis. The most prevalent subtypes of thalassemia that cause severe anemia are beta-thalassemia major or double heterozygosity for beta-thalassemia and hemoglobin (Hb) E. The details of thalassemia genetics, laboratory and clinical phenotypes, and general management are presented in other comprehensive resources.

Iron overload in persons with severe thalassemia syndromes is a major cause of morbidity due to endocrinopathy (especially hypogonadism and diabetes mellitus), liver disease, and cardiomyopathy. Many patients have increased susceptibility to severe or recurrent infections due to bacteria and other microbes (Chapter 7). Cardiomyopathy due to cardiac siderosis is the leading cause of death in patients with severe beta-thalassemia. Iron overload in patients with thalassemia is usually caused by increased absorption of dietary iron and retention of additional iron from chronic erythrocyte transfusion administered to alleviate severe anemia. This chapter is devoted principally to iron overload and related abnormalities in patients with severe thalassemia.

Development of iron overload

Mechanisms that enhance iron absorption

In severe beta-thalassemia, deficient globin-chain production results in anemia and ineffective erythropoiesis.