Alpha-Thalassemia: Diversity of Clinical Phenotypes and Update on the Treatment

Abstract

One of the more common single-gene disorders worldwide is α-thalassemia, carriers of which are found at variable frequencies (>1%) across all tropical and subtropical countries. Two linked α-globin genes on each allele of chromosome 16 regulate α-globin chain production. Deletion of one or more α-globin genes is the most frequent molecular defect found in α-thalassemia, whereas non-deletional mutations also occur, leading to unstable α-globin chains. HbH is the most common clinically important α-thalassemia disease and occurs when three α-globin genes are deleted/mutated, leaving only one copy of the gene intact. HbH can be divided into deletional (--/-α) and non-deletional genotypes (--/αTα). Whereas clinical phenotypes of the former are usually homogenously mild to moderate, those of the latter can be diverse. As HbH disease is particularly prevalent in Southeast Asia and some parts of the Mediterranean region, where β-thalassemia is also prevalent, affected patients are sometimes left undertreated. Therefore, hematologists and general physicians need to be educated to provide optimal disease monitoring and early identification of those with more severe phenotypes. Some issues regarding transfusion and iron chelation management differ from those of β-thalassemia, and these need to be recognized. Hb Bart’s hydrops fetalis syndrome (BHFS) is the most severe form of α-thalassemia; affected patients lack production of α-globin chains. Recent advances in fetal medicine and neonatal intensive care have made it possible for BHFS to no longer constitute a universally fatal disorder. Transfusion and chelation strategies for rare survivors are distinct and require updating.