Alpha Globin Gene Mutation: A Major Determinant of Hydroxyurea Response in Transfusion-Dependent HbE-β-Thalassaemia

Abstract

Thalassaemias are the most common inherited autosomal recessive single gene disorders characterised by chronic hereditary haemolytic anaemia due to absence or reduced synthesis of one or more of the globin chains. Haemoglobin E (HbE)-β-thalassaemia is the genotype responsible for approximately one-half of all cases of severe β-thalassaemia worldwide. This study proposes to evaluate response of hydroxyurea in reducing transfusion requirements of severe HbE-β-thalassaemia patients, and its correlation with foetal haemoglobin (HbF) level and α-mutation. Hydroxyurea was started at a baseline dose in 82 transfusion-dependent HbE-β-thalassaemia patients. HbF levels and %F-cells were measured. β-Thalassaemia mutations and α-globin gene deletions and triplications were detected by amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) and Gap-PCR, respectively. Patients were categorised as good (41.5%), moderate (31.7%), and poor responders (26.8%) based on their decrease in transfusion requirements. Nine patients were excellent responders who became transfusion independent. The mean increase in HbF levels and %F-cells after therapy was correlated with decrease in transfusion requirements. Patients having a deletion of the α-globin gene were better responders. The response was proportional to the number of α-globin gene deletions. We conclude that hydroxyurea treatment decreases transfusion requirements, and the response correlates with α-globin gene deletions.