The correlation of α-globin gene mutations and the XmnI polymorphism with clinical severity of Hb E/β-thalassemia.

Clinical severity assessment and molecular analysis of β-, α-globin genes and the -158 (C > T) XmnI polymorphism of the (G)γ-globin gene were performed in 80 pediatric patients with Hb E (HBB: c.79G > A)/β-thalassemia (β-thal) to investigate the effects of coinheritance of α-thalassemia (α-thal) and other molecular determinants on their clinical severity. The mean age was 9.4 ± 5.1 years. By using clinical severity score, 35 (43.8%), 27 (33.8%) and 18 cases (22.5%) had moderate, mild and severe disease, respectively. Nine β-thal mutations were identified. All were β⁰ or severe β⁺ mutations. Five patients (6.3%) had coinherited α⁰-thal. All five patients had mild disease with baseline hemoglobin (Hb) values of 7.9 ± 1.5 g/dL, mild hepatosplenomegaly and close-to-normal growth. Only one required a red blood cell transfusion. The disease severity was significantly different among the groups with and without α-thal (p = 0.025), but was not different among the groups with or without the XmnI polymorphism (p = 0.071). This study demonstrates that coinheritance of α⁰-thal alleviates the degree of disease severity in Hb E/β-thal. All our patients with coinherited α⁰-thal have mild disease.