EFFECT OF ALPHA-THALASSEMIA TRAIT AND ENHANCED GAMMA-CHAIN PRODUCTIONON DISEASE SEVERITY IN BETA-THALASSEMIA MAJOR AND INTERMEDIA

One hundred and twenty patients with homozygous beta thalassaemia were selected to determine the clinical effects of certain genetic factors which may modify disease severity. Genetic analysis defined specific beta thalassaemia mutations, the alpha thalassaemia genotype, and the presence of an XmnI restriction enzyme site, associated with increased fetal haemoglobin (HbF) production under certain conditions. Genotypi c data with globin chain synthesis were related to the age when regula r transfusions began and subsequent pubertal development. This study s howed that the major determinants of disease severity in beta thalassa emia were the beta thalassaemia mutations, with co-inheritance of alph a thalassaemia trait and co-inheritance of a high HbF determinant acti ng as ameliorating factors. The presence of an alpha thalassaemia dele tion significantly reduced initial disease severity, although the effe ct on pubertal development was less clear. It is concluded that detail ed genetic analysis should be performed in all newly diagnosed patient s with thalassaemia. This, in conjunction with clinical assessment, wi ll help to predict disease severity and prognosis.