6 - Hemoglobinopathies and Thalassemias

Abstract

This chapter presents a brief outline of the structure, function, and biosynthesis of the normal human hemoglobins and then discusses the current knowledge of the clinical diseases associated with defects in globin synthesis, their molecular pathology, diagnosis, and treatment. The different types of hemoglobin variants are summarized, with an emphasis on those that exhibit a clinically significant change in their functional properties. A major portion of the chapter is devoted to the sickle cell disorders, describing the genetics and geographical distribution of HbS, the clinical aspects of sickle cell disease and its diagnosis, treatment and prevention, and a brief review of the interactions of HbS with other hemoglobinopathies. Emerging pharmacologic and gene therapy approaches for the treatment of sickle cell disease are also reviewed in detail. Finally, the molecular basis of the alpha and beta thalassemias is reviewed, with a brief discussion of the molecular effects of each category of gene defect. The clinical features of the thalassemia are described, and the process of carrier identification is outlined, together with current approaches to therapy and prevention, including the latest updates on curative and gene therapy approaches.