α−thalassaemia: a genotype–phenotype correlation and management

Abstract

Throughout the world, α−thalassaemia represents the most common monogenic disorder in man [1]. A large number of mutations (mainly deletions and a few nucleotide substitutions) of the human α-globin cluster have been described which interact to produce one of three broad phenotypes, α-thalassaemia heterozygote, Hb H disease and Hb Bart's hydrops fetalis [2]. In terms of public health, α-thalassaemia trait only causes a mild anaemia and Hb Bart's hydrops fetalis is usually fatal in late gestation [2-4]. In contrast, Hb H disease is a relatively common cause of thalassaemia in individuals of Southeast Asian, Middle Eastern and Mediterranean origins and is associated with a variety of clinically important complications [3, 5]. This review will focus on the molecular basis of α−thalassaemia in general and more specifically illustrate a recent development in molecular characterization of several, including novel, α−thalassaemia alleles found recently. The complexity of globin genotype–phenotype correlation in α−thalassaemia disease will be discussed with particular regard to patients with Hb H disease.