Transfusion requirements and complication rate in β-thalassemia intermedia due to heterozygous β-globin gene mutation and triplicated α-globin genes

Introduction: The heterozygous condition for β-thalassemia mutation associated with an extra functional α-globin gene can produce a Thalassemia Intermedia (TI) phenotype. This genotype is the second in frequency in the French Thalassemia Registry NaThalY that prospectively collects laboratory and clinical data.

Materials and methods: The present report analyses transfusion needs, iron overload (ferritin, hepatic and cardiac iron concentrations), and complication rates in 45 patients included in NaThalY and presenting a heterozygous β⁰ or β⁺ -thalassemia mutation associated with a triplication at HBA locus. This cohort was compared to a cohort of patients with TI due to mutations in the beta-globin gene only and included in the French registry.

Results: Patients with an extra functional α-globin gene showed a less severe anemia, lower transfusion needs and lower complication rates than those with TI related to the β-globin gene only. Nevertheless, some of them displayed complications such as cholelithiasis or extramedullary hematopoiesis. In addition, one third of the cohort needed transfusions and another third was under iron chelation.

Conclusion: The genotype associating a heterozygous β⁰ or β⁺ -thalassemia mutation with a triplication at HBA locus should be accurately diagnosed as it could lead to symptomatic anemia and to potential iron overload and iron-related complications even in patients with no transfusion need.