Beta-Thalassemia in Spain: Results From the National Thalassemia Registry and Molecular Analysis of Patients With Transfusion-Dependent Thalassemia

Abstract

BACKGROUND: Beta-thalassemia is a genetically heterogeneous hemoglobinopathy with marked clinical variability. In Spain, comprehensive nationwide data on transfusion-dependent beta-thalassemia (TDT) remain limited, particularly regarding molecular characterization. METHODS: This observational study analyzed data from the National Thalassemia Registry of the Spanish Society of Hematology and Hemotherapy (SEHH). Between November 2022 and February 2025, 147 patients with beta-thalassemia from 42 hospitals were registered; this report focuses on 78 patients with TDT. Clinical, transfusion, and biochemical data were collected, and molecular analysis of the HBB and HBA genes was performed using Sanger sequencing, next-generation sequencing, and complementary techniques. Genotypes were classified according to the degree of beta-globin synthesis reduction. RESULTS: The mean age of TDT patients was 34.3 years, and 73.1% were of Spanish origin. Patients received a mean of 31.4 packed red blood cell units per year. Splenectomy had been performed in 35.9% of cases. Most patients showed adequate iron overload control, with median serum ferritin levels below 1000 ng/mL. Twenty-four different HBB mutations were identified; the most frequent were CD39 (C > T), IVS-1-nt1 (G > A), IVS-1-nt110 (G > A), IVS-1-nt6 (T > C), and IVS-1-nt1 (G > T), accounting for 75% of alleles. Genotype distribution was 55.2% ?(0)/?(0), 30.3% ?(0)/?(+), and 14.4% ?(+)/?(+). Patients with ?(+)/?(+) genotypes had significantly lower ferritin levels. CONCLUSIONS: This nationwide registry highlights the genetic and clinical heterogeneity of TDT in Spain and underscores the value of molecular characterization for patient management, genetic counseling, and future therapeutic strategies.