Hemoglobinopathies and Thalassemia in Northeast India: A Scoping Review of Disease Burden, Mutation Spectrum, and Gaps in Molecular Genetic Evidence

Abstract

Abstract

Hemoglobinopathies are among the most prevalent inherited monogenic disorders globally and represent a major public health challenge in India, which contributes substantially to the global disease burden. Marked regional heterogeneity exists across the country, and Northeast India constitutes a genetically distinct region characterized by a high prevalence of hemoglobin E (HbE), significant tribal population diversity, and a disproportionate burden of compound hemoglobin disorders. This scoping review aimed to systematically map the available evidence on the burden, geographic distribution, diagnostic patterns, and molecular spectrum of hemoglobinopathies globally and in India, with a primary analytical focus on Northeast India. A scoping review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) standards. We conducted extensive literature searches in PubMed, Google Scholar, and Web of Science and supplemented these with citation tracking. We included primary studies providing epidemiological, hematological, or molecular data on hemoglobinopathies. Eligible studies were population- and hospital-based. Data on research setting, demographic characteristics, diagnostic procedures, distribution of hemoglobin variants, and mutation profiles were extracted and analyzed using descriptive and thematic synthesis. Forty-five studies were included. Of these, 27 were undertaken exclusively in Northeast India, 11 were pan-Indian or multi-regional studies that published stratified data for Northeast Indian populations, and seven provided global or Southeast Asian contextual evidence. HbE was the most common structural hemoglobin variant observed across all districts of Northeast India in heterozygous, homozygous, and compound heterozygous states. HbE-β-thalassemia was consistently recognized as a primary cause of clinically significant disease, whereas reports of HbS-β-thalassemia were less frequent and largely limited to isolated clinical and hospital-based reports. The spectrum of β-thalassemia mutations in Northeast India overlapped considerably with pan-Indian patterns, with recurrent mutations such as IVS-I-5 (G>C), IVS-I-1 (G>T), and codon 41/42 (-CTTT), in addition to rare and region-specific mutations. Hospital-based and molecular investigations suggest that compound hemoglobinopathies are underdiagnosed and underline the modifying influence of α-thalassemia and other hereditary factors. A number of studies also reported a disproportionate burden among tribal populations, reflecting founder effects, endogamy, and disparities in access to healthcare. Northeast India exhibits a distinct hemoglobinopathy landscape dominated by HbE and compound hemoglobin disorders, with unique molecular and clinical characteristics. These findings underscore the need for region-specific screening strategies, expanded molecular diagnostic panels, and targeted public health interventions tailored to the genetic and sociocultural context of Northeast India.