Severe thalassaemia intermedia caused by interaction of homozygosity for α-globin gene triplication with heterozygosity for β° thalassaemia

A 3-year-old child was evaluated for β-thalassaemia intermedia. Molecular characterization including β-globin gene sequence analysis revealed heterozygosity for a single β-thalassaemia mutation, IVSI nt1 (G→A). In addition the patient was found to be homozygous for α-globin gene triplication (ααα(anti 3.7)/ααα(anti 3.7)). The propositus has a significantly more severe phenotype than has been previously reported with this combination of genetic defects. In contrast, four individuals heterozygous for both triplicated α and for β thalassaemia had a phenotype of thalassaemia minor, and a fifth had very mild thalassaemia intermedia.