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

• Published in: Hemoglobin Vol. 44; no. 1; pp. 1 - 9
• Main Authors: Belisário, André R., Carneiro-Proietti, Anna B., Sabino, Ester Cerdeira, Araújo, Aderson, Loureiro, Paula, Máximo, Cláudia, Flor-Park, Miriam V., Rodrigues, Daniela D.O.W., Ozahata, Mina Cintho, McClure, Christopher, Mota, Rosimere Afonso, Gomes Moura, Isabel C., Custer, Brian, Kelly, Shannon
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-01-2020
• Subjects: Adolescent; Adult; Alleles; Anemia, Sickle Cell - diagnosis; Anemia, Sickle Cell - epidemiology; Anemia, Sickle Cell - genetics; Anemia, Sickle Cell - pathology; beta-Globins - genetics; beta-Thalassemia - diagnosis; beta-Thalassemia - epidemiology; beta-Thalassemia - genetics; beta-Thalassemia - pathology; Brazil - epidemiology; Child; Clinical events; Codon; Cohort Studies; DNA Mutational Analysis; Female; Gene Expression; Gene Frequency; Genotype; Hb S/β; Hemoglobin, Sickle - genetics; Humans; Incidence; Male; Mutation; Phenotype; Severity of Illness Index; sickle cell disease; thal; thalassemia (Hb S/β; thalassemia mutation; Brazil; Hb S/β+-thalassemia (Hb S/β+-thal); Hb S/β0-thalassemia (Hb S/β0-thal); Clinical events; thalassemia mutation; sickle cell disease
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1080/03630269.2020.1731530

We described the clinical, laboratory and molecular characteristics of individuals with Hb S (HBB: c.20A>T)/β-thalassemia (Hb S/β-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 β-thal mutation. Patients were classified as Hb S/β
0
-thal, Hb S/β
+
-thal-severe or Hb S/β
+
-thal based on prior literature and databases of hemoglobin (Hb) variants. Characteristics of patients with each β-thal mutation were described and the clinical profile of patients grouped into Hb S/β
0
-thal, Hb S/β
+
-thal and Hb S/β
+
-thal-severe were compared. Of the 2793 patients enrolled, 84 (3.0%) had Hb S/β
0
-thal and 83 (3.0%) had Hb S/β
+
-thal; 40/83 (48.2%) patients with Hb S/β
+
-thal had mutations defined as severe. We identified 19 different β-thal mutations, eight Hb S/β
0
-thal, three Hb S/β
+
-thal-severe and eight Hb S/β
+
-thal. The most frequent β
0
and β
+
mutations were codon 39 (HBB: c.118C>T) and IVS-I-6 (T>C) (HBB: c.92+6T>C), respectively. Individuals with Hb S/β
0
-thal had a similar clinical and laboratory phenotype when compared to those with Hb S/β
+
-thal-severe. Individuals with Hb S/β
+
-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/β
+
-thal. Likewise, individuals with Hb S/β
+
-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.