Clinical, laboratory, and molecular characteristics of a cohort of children with hemoglobinopathy S/beta-thalassemia.

Introduction: Hemoglobinopathy Sβ-thalassemia (HbSβ-thal) has a wide range of clinical and laboratory severity. There is limited information on the natural history of HbSβ-thal and its modulating factors. We described the molecular, hematological, and clinical characteristics of a cohort of children with HbSβ-thal and estimated its incidence in Minas Gerais, Brazil.

Methods: Laboratory and clinical data were retrieved from medical records. Molecular analysis was performed by HBB gene sequencing, PCR-RFLP, gap-PCR, and MLPA.

Results: Eighty-nine children were included in the study. Fourteen alleles of β-thal mutations were identified. The incidence of HbSβ-thal in the state was 1 per 22,250 newborns. The most common β-haplotypes were CAR and Benin. The most frequent β-haplotypes were V, II, and I. Coexistence of 3.7 kb HBA1/HBA2 deletion was present in 21.3 % of children. β-thalassemia mutations were associated with several clinical and laboratory features. In general, the incidence of clinical events per 100 patient-years was similar for children with HbSβ-thal, IVS-I-5 G>A, and IVS-I-110 G>A. Children with HbSβ-intermediate phenotypes had a more severe laboratory and clinical profile when compared with those with HbSβ-mild ones. β-haplotypes and α-thalassemia did not meaningfully influence the phenotype of children with HbSβ-thal.

Conclusion: The early identification of β-thalassemia alleles may help the clinical management of these children.