Hb S/?-Thalassemia in the REDS-III Brazil Sickle Cell Disease Cohort: Clinical, Laboratory and Molecular Characteristics.

ABSTRACT: We described the clinical, laboratory and molecular characteristics of individuals with Hb S (HBB: c.20A>T)/?-thalassemia (Hb S/?-thal) participating in the Recipient Epidemiology and Donor Evaluation Study (REDS-III) Brazil Sickle Cell Disease cohort. HBB gene sequencing was performed to genotype each ?-thal mutation. Patients were classified as Hb S/?⁰-thal, Hb S/?⁺-thal-severe or Hb S/?⁺-thal based on prior literature and databases of hemoglobin (Hb) variants. Characteristics of patients with each ?-thal mutation were described and the clinical profile of patients grouped into Hb S/?⁰-thal, Hb S/?⁺-thal and Hb S/?⁺-thal-severe were compared. Of the 2793 patients enrolled, 84 (3.0%) had Hb S/?⁰-thal and 83 (3.0%) had Hb S/?⁺-thal; 40/83 (48.2%) patients with Hb S/?⁺-thal had mutations defined as severe. We identified 19 different ?-thal mutations, eight Hb S/?⁰-thal, three Hb S/?⁺-thal-severe and eight Hb S/?⁺-thal. The most frequent ?⁰ and ?⁺ mutations were codon 39 (HBB: c.118C>T) and IVS-I-6 (T>C) (HBB: c.92+6T>C), respectively. Individuals with Hb S/?⁰-thal had a similar clinical and laboratory phenotype when compared to those with Hb S/?⁺-thal-severe. Individuals with Hb S/?⁺-thal-severe had significantly lower total Hb and Hb A levels and higher Hb S, white blood cell (WBC) count, platelets and hemolysis markers when compared to those with Hb S/?⁺-thal. Likewise, individuals with Hb S/?⁺-thal-severe showed a significantly higher occurrence of hospitalizations, vaso-occlusive events (VOE), acute chest syndrome (ACS), splenic sequestration, blood utilization, and hydroxyurea (HU) therapy.

SUBMITTER: Belisario AR 

PROVIDER: S-EPMC7225056 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature