Challenges faced in screening for thalassemia and other hemoglobinopathies in a North Indian population

Hemoglobinopathies are a common group of inherited disorders contributing significantly to the global healthcare burden, particularly in low and middle-income countries (LMICs) such as India. This prospective cross-sectional study aimed to investigate the epidemiological, clinical, and genetic aspects of hemoglobinopathies in the antenatal population attending a tertiary care hospital in Delhi. A total of 7077 antenatal women were investigated over four years, revealing an overall prevalence of Beta Thalassemia Trait (BTT) of 4.55%. The screening algorithm involved a complete blood count (CBC) and High Performance Liquid Chromatography (HPLC) for all the women, followed by mutation testing using Multiplex amplification refractory mutation system - polymerase chain reaction (ARMS PCR) for four common mutations: IVS1-5 (G > C), CD41/42 -TTCT, CD8/9 +G, and Del 619 bp. Multiplex ligation dependent probe amplification assay (MLPA), ARMS PCR and Sanger sequencing were used to identify other mutations. In cases where abnormal High Peformance Liquid Chromatography (HPLC) results were found, further testing of the husband was conducted to guide counselling and decisions regarding prenatal testing. IVS1-5 (G > C) was identified as the most common mutation. Hemoglobin E (HbE) with CD26 (G > A) exhibited the highest hemoglobin and HbA2 values amongst all mutations screened for. The study underscores the challenges of using RBC indices to diagnose BTT, due to marked overlap with Nutritional Deficiency Anemia (NDA). Similar issues were observed with HbD and HbE due to their relatively high MCV and MCH values. An algorithm for antenatal screening and diagnosis for LMIC is proposed but, given these caveats, its value remains to be proven. The study provides data on the relative distribution of hemoglobinopathy mutations in the antenatal population in North India, and revealed the problems of detecting BTT or hemoglobinopathy in this population with a CBC due to the widespread prevalence of NDA. It emphasized the challenges of targeted screening strategies and genetic counselling to effectively reduce the prevalence of thalassemia in North India.