A novel molecular basis for β thalassemia intermedia poses new questions about its pathophysiology

Abstract

AbstractDuring a study of the molecular basis for severe forms of β thalassemia in Sri Lanka, 2 patients were found to be heterozygous for β thalassemia mutations. Further analysis revealed that one of them has a previously unreported molecular basis for severe thalassemia intermedia, homozygosity for quadruplicated α globin genes in combination with heterozygous β thalassemia. The other is homozygous for a triplicated α globin gene arrangement and heterozygous for β thalassemia. Their differences in clinical phenotype are explainable by the interaction of other genetic factors and, in particular, their early management. The clinical course of the 2 propositi underlines the importance of full genotyping and a long period of observation before treatment is instituted, particularly in patients with β thalassemia intermedia associated with extended α globin gene arrangements. The hemoglobin (Hb) F levels in these patients with severe β thalassemia intermedia, compared with other forms of this condition in the Sri Lankan population and elsewhere, are unusually low, a consistent finding in extended α globin gene interactions and in dominant β thalassemia, raising the possibility that increased levels of HbF production in β thalassemia may require mutations at both β globin gene loci.