In α–thalassemia –

Alpha - thalassemia People who do not produce enough alpha globin chain have alpha - thalassemia. Alpha globin chain is made by four genes, each gene contributes to 25% of the a-globin chains. The severity of a-thalassemia varies greatly depending on the number of α-globin genes affected - I)  Silent carrier state Single α-globin gene is deleted. These individuals are completely asymptomatic. ii) α-thalassemia trait Two α-globin genes are deleted These individuals are asymptomatic with some red cell abnormalities like β-thalassemia minor. iii) HbH disease Three genes of the a-globin chain are deleted. With only one gene, the synthesis of α-chain is markedly reduced and tetramers of excess β-globin called HbH, form. HbH has an extremely high affinity for oxygen and therefore is not useful for oxygen exchange, leading to tissue hypoxia disproportionate to the level of haemoglobin. Patients have moderate to severe anaemia that may require an occasional blood transfusion. iv) Hydrops fetalis Deletion of all four α-globin genes. In the fetus, excess γ-globin chains form tetramers, known as haemoglobin harts. Hemolgobin bart has such a high affinity for oxygen that it delivers almost no oxygen to tissues. Most individuals die before or shortly after birth. In utero blood transfusion have allowed the birth of children with hydrops fetalis who then require life long blood transfusions.