Molecular mechanism accounting for milder types of thalassemia major

We carried out alpha-globin gene analysis by restriction endonuclease mapping in 91 Sardinians with homozygous transfusion-dependent beta 0-thalassemia and correlated the clinical findings with the alpha-globin genotype. In patients (n = 6) with deletion of two alpha-globin structural genes, disease onset and transfusion dependence occur later than in those (n = 50) with a full complement of alpha-globin genes. There was no statistically significant difference in the group of patients (n = 35) with deletion of only one alpha-globin gene. Patients with deletion of two alpha-globin genes had significantly higher Hb A2 levels than those with a full complement of alpha-structural genes and those with deletion of a single alpha-globin gene. From this and other studies, it seems that the deletion of two alpha-globin structural genes may convert the common severe clinical picture associated with homozygous beta 0-thalassemia to milder forms, ranging from a later occurring but still transfusion-dependent type to a non-transfusion-dependent form.