Frequencies and phenotypic consequences of association of α- and β-thalassemia alleles with sickle-cell disease in Bahrain

Introduction: Bahrain has high prevalence rates of sickle cell and thalassemia in the population. This study reports the frequencies and phenotypic characteristics of alpha- and/or beta-thalassemia associated with sickle-cell disease (SCD) in a tertiary care hospital. Methods: Adult SCD patients (n = 200) were screened for the common alpha- and beta-thalassemia alleles prevalent in the region using molecular techniques. Results of CBC, hemoglobin analysis, and average annual frequencies of severe pain episodes and numbers of transfused red cell units were documented. Results: Patients were grouped on the basis of molecular studies as sickle-cell anemia (SS, n = 131), SS/alpha-thalassemia with three normal genes (n = 27), SS/alpha-thalassemia with two normal genes (n = 11), sickle-beta-thalassemia (S beta, n = 23), and Sb with co-inherited alpha-thalassemia (n = 8). Identified alpha-thalassemia determinants were -alpha(3.7) (n = 52), -alpha(4.2) (n = 4), alpha(T-Saudi)alpha (n = 1), and alpha(Hph) alpha (n = 1). All beta-thalassemia alleles were beta(0) defects. Sickle-thalassemia association resulted in higher hemoglobin, hematocrit, and erythrocyte counts with reduced MCV and reticulocytes. Significant clinical associations were as follows: increased severe pain frequency with alpha-thalassemia (three-gene group); red cell transfusion with beta-thalassemia alleles and female gender. Conclusion: One-third of patients with SCD co-inherited alpha- and/or beta-thalassemia alleles and these associations explained some of the observed phenotypic variability. A low prevalence of nondeletion alpha-thalassemia alleles was observed in these patients. The most significant disease amelioration occurred in SCD associated with two alpha-thalassemia alleles.