Hematological and Molecular Spectrum of Hemoglobinopathies in the Tharu Population of Nepal

Hemoglobinopathies are inherited disorders of hemoglobin, most notably sickle cell anemia and thalassemia. These conditions result from mutations in the globin genes, leading either to structural abnormalities in the globin chains or to reduced synthesis of normal globin chains. Hemoglobinopathies is a worldwide health problem according to the World Health Organization; it affects mostly the indigenous Tharu groups in Nepal. Both the global and local rates of illness and death associated with these diseases are on the rise. The objective of this study was to assess the presence of hemoglobinopathies and common mutations of the beta-globin gene within the Tharu population in western Nepal. A cross-sectional study of 1,400 Tharu individuals was conducted among individuals obtained through hospitals within the Banke district, Bardiya district, and Kailali district in western Nepal. A thorough hematological analysis was done with the use of a Sysmex XN-350 analyzer. Hemoglobin variants were detected via high-performance liquid chromatography (HPLC). The molecular characterization of the seven most common mutations of {beta}-thalassemia was performed on a subset of 20 confirmed cases by using a real-time PCR kit.The total number of cases diagnosed with hemoglobinopathies was 14.43% (n=202 out of 1,400). Sickle cell trait (HbAS) was reported as the most prevalent type of Hemoglobinopathies (8.50% of population), followed by {beta}-thalassemia trait (4.00%). In addition to these disorders were sickle cell disease (HbSS), HbE trait, and compound heterozygous states. Hematological parameters differed significantly across types of hemoglobinopathies, and the patterns of microcytic, hypochromic, and hemolytic anemia were also distinct. Commonly documented symptoms included fatigue and joint pain (42.5% and 23.1%, respectively). Molecular characterization of {beta}-thalassemia cases demonstrated that most individuals were compound heterozygotes with IVS1-6 (T>C) as the most prevalent variant. The research identified that the Tharu population in western Nepal has a significant burden of hemoglobinopathies (especially sickle cell trait and {beta}-thalassemia), highlighting the requirement for appropriate screening programs, genetic counseling and public health strategies to help manage and prevent these conditions within this particular region.