Influence of Alpha-thalassemia −3.7kb Mutation (αα/-α and -α/-α) upon Clinical Outcome of Homozygous Sickle Cell Disease

Abstract

Alpha thalassemia (α-thal), fetal haemoglobin (HbF) and beta-globin haplotype are considered classical genetic disease modifiers in Sickle cell disease (SCD) causing clinical heterogeneity. Nevertheless their impact on clinical emergence and disease progression is still elusive. In this retrospective study, we have estimated the correlation of deletional α-thalassemia and associated factors like fetal haemoglobin (HbF) in patients with homozygous SCD from Odisha and Chhatisgarh, two of the central-eastern states of India. Six different types of deletional α-thalassemia were studied by Molecular analysis using gap PCR (N= 267) and HbF% by Cationic exchange High performance Liquid Chromatography (CE- HPLC). Haematological, biochemical and radiological investigations were used to distinguish associated complications in the patients along with an account of malarial infections. Out of the total, 25.3% (n=68) SCD patients had deletional α-thalassemia presented better clinical profiles and haematological indices. Decrease in painful crisis (x2-12.5, p<0.05), chronic renal failure (CRF) along with priapism and leg ulcer were observed in alpha-thalassemia −3.7-kb mutation (αα/-α and -α/-α) in comparison to control SCD group. Females with single α- gene deletions (αα/-3.7α) had significantly raised HbF% than corresponding males with a better clinical status and less medical consultations or hospitalizations. Thus, elevated level of HbF and presence of α-thalassemia mutations were well correlated with better sickle-cell RBC rheology, indicating an overall improved clinical picture of homozygous SCD.