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 particular emphasis on those that exhibit a clinically significant change in their functional properties—the unstable hemoglobins, variants with altered oxygen affinity and the M hemoglobins that result in congenital cyanosis. A major portion of the chapter is devoted to the sickle-cell disorders, describing the genetics and geographical distribution of Hb S, the clinical aspects of sickle-cell disease and its diagnosis, treatment and prevention, and a brief review of the interactions of Hb S with other hemogobinopathies. Finally, the molecular basis of the alpha and beta thalassemias is reviewed, with an up-to-date listing of the mutations and 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 the most commonly used methods of molecular identification of the thalassemia mutations, and the current approaches to therapy and prevention.