Alpha-thalassemia

Alpha-thalassemia is one of the most common hemoglobin genetic abnormalities and is caused by the reduced or absent production of the alpha globin chains. Alpha-thalassemia is prevalent in tropical and subtropical world regions where malaria was and still is epidemic, but as a consequence of the recent massive population migrations, alpha-thalassemia has become a relatively common clinical problem in North America, North Europe, and Australia. Alpha-thalassemia is very heterogeneous at a clinical and molecular level. Four clinical conditions of increased severity are recognized: the silent carrier state, the alpha-thalassemia trait, the intermediate form of hemoglobin H disease, and the hemoglobin Bart hydrops fetalis syndrome that is lethal in utero or soon after birth. Alpha-thalassemia is caused most frequently by deletions involving one or both alpha globin genes and less commonly by nondeletional defects. A large number of alpha-thalassemia alleles have been described and their interaction results in the wide spectrum of hematological and clinical phenotypes. Genotype-phenotype correlation has been only partly clarified. Carriers of alpha-thalassemia do not need any treatment. Usually, patients with hemoglobin H disease are clinically well and survive without any treatment, but occasional red blood cell transfusions may be needed if the hemoglobin level suddenly drops because of hemolytic or aplastic crisis likely due to viral infections. Hemoglobin Bart hydrops fetalis syndrome currently has no effective treatment although attempts at intrauterine transfusion and hematopoietic stem cell transplantation have been made. Genet Med 2011:13(2): 83-88.