Iron-refractory iron-deficiency anemia in pregnancy associated with a novel TMPRSS6 missense variant (c.248T>G): A case report from North India

Iron-deficiency anemia remains the most frequent cause of anemia in pregnancy and is usually amenable to treatment with oral or intravenous iron. Nonetheless, a minority of patients exhibit poor therapeutic response despite adequate dosing and compliance, warranting evaluation for uncommon etiologies such as iron-refractory iron-deficiency anemia (IRIDA). IRIDA is a rare inherited disorder with an autosomal recessive pattern, caused by mutations in the TMPRSS6 gene that lead to inappropriate hepcidin activity and disrupted iron regulation. Here, we present the case of a pregnant Indian woman with persistent microcytic hypochromic anemia that failed to improve with oral iron and showed only modest response to parenteral therapy. Biochemical findings revealed reduced serum iron and low transferrin saturation, indicating defective iron handling. Owing to the refractory nature of the condition, genetic testing was performed, which identified compound heterozygous missense mutations in the TMPRSS6 gene, including a novel variant (c.248T>G). Management included intravenous iron supplementation along with close antenatal surveillance, resulting in stabilization of hemoglobin levels and a satisfactory maternal and fetal outcome. This case emphasizes the importance of considering IRIDA in cases of unexplained treatment-resistant iron-deficiency anemia and highlights the role of molecular diagnostics in establishing a definitive diagnosis.