THALASSEMIA INTERMEDIA TODAY

Recently the molecular bases of thalassemia intermedia have been elucidated in several populations. In general this attenuated, non-transfusion dependent form of homozygous .beta.-thalassemia is mainly determined by a) the co-inheritance of deletion .alpha.-thalassemia; b) the presence of the so-called mild .beta.-thalassemia mutations; and more rarely, c) the inheritance of genetic conditions able to enhance the .gamma.-globin chain expression in adult life. Although there are several complex genetic and acquired interactions involved in the wide clinical heterogeneity of thalassemia intermedia, data in Italians indicate a definite genotype-phenotype relationship in conditions such as the co-inheritance of at least two .alpha.-thalassemia genes in severe and mild homozygous .beta.-thalassemia; the molecular homozygosity or double heterozygosity for the -87, -101 and IVS1(nt6) .beta.+-thalassemia mutations; and the coexistence of structural .gamma.-globin gene defects, i.e. Sicilian and Sardinian .delta..beta.-thalassemias, deletional and non-deletional Hereditary Persistence of Fetal Hemoglobin and the polymorphism for the -158 XmnI G.gamma. restriction site. Thalassemia intermedia resulting from the inheritance in heterozygous .beta.-thalassemia of triple .alpha.-globin gene complex or the presence of dominant .beta.-thalassemia is also described and the role of these new informations in genetic counselling is discussed.