Molecular spectrum of alpha thalassemia: An unrecognised blood disorder in Nepal

Abstract Background: Thalassemia and hemoglobinopathies are inherited disorders characterized by impaired hemoglobin synthesis and chronic anemia. Globally, an estimated 7% of the population carries a hemoglobinopathy. In Nepal, while beta thalassemia and sickle cell disease have been relatively well-documented, alpha thalassemia remains understudied. To address this gap, we conducted the first study in Nepal investigating both deletional and non-deletional forms of alpha thalassemia among individuals referred for evaluation of microcytic, hypochromic erythrocytes with normal or borderline Hb A₂ levels. Methods: Eighty-one individuals (36 males, 45 females) with low red cell indices (MCV <80 fL, and MCH <27 pg) along with normal or subnormal Hb A2 were studied. HbA1 and HbA2 genes were evaluated for deletion, duplication and point mutation by Multiplex Ligation dependent Probe Amplification and Sanger sequencing. Results: The deletional alpha genes were identified in 56.8% of cases. The most common deletion was -α3.7 and it was found in 43 patients (53.08%), of which 24 were homozygous (55.81%) and 19 heterozygous (44.18%). Among the -a3.7 deletion 46.51 % were male and 53.48 % were female . A smaller subset (3.70%) carried the -α 4.2deletion. Similarly point mutations were identified in four individuals. The most common Point mutation was Hb. Sun prairie and Hb A2 : c*93_*94delAA. Conclusion: This study is the first to report the presence of non-deletional forms of alpha thalassemia in Nepal, alongside a notably high prevalence of the -α3.7 gene deletion among affected individuals. Based on these findings , population based studies are required to explore the prevalance and other genetic landscapes in alpha thalassemia.