Prenatal Diagnosis of Compound Heterozygous Beta-Thalassemia: A Report of Two Cases

Beta (β)-thalassemia and related hemoglobinopathies remain a major genetic health burden in India. Prenatal diagnosis plays a crucial role in preventing recurrence of severe disease in high-risk couples, particularly those with previously affected children. We report two cases of prenatal diagnosis performed by mid-trimester amniocentesis in couples with prior children affected by severe β-globin disorders. In Case 1, molecular analysis of fetal DNA revealed compound heterozygosity for HBB c.92G>C (β⁺) and HBB c.126_129del (β⁰), consistent with severe β-thalassemia. In Case 2, fetal testing demonstrated HbE/β-thalassemia due to compound heterozygosity for HBB c.79G>A (HbE) and HBB c.92+5G>C (β⁰). Both diagnoses were established using PCR-based amplification and Sanger sequencing after exclusion of maternal DNA contamination. Given the severe clinical phenotype observed in previously affected siblings and following detailed genetic counseling, both couples opted for medical termination of pregnancy. These cases underscore the importance of molecular prenatal diagnosis in accurately identifying severe compound heterozygous hemoglobinopathies. Early carrier detection, definitive fetal genotyping, and timely counseling remain essential strategies for reducing the burden of β-thalassemia in high-prevalence regions.