Inherited microcytic anemias due to disorders of iron and heme metabolism: An updated clinical review.

Microcytic anemia is among the most common hematological abnormalities in clinical practice and is usually attributable to iron deficiency, thalassemia traits, or anemia of inflammation. A small but clinically important subset of patients, however, has inherited disorders of iron metabolism or heme synthesis presenting with persistent, unexplained, familial, or iron-refractory microcytosis. Over the past decade, advances in the understanding of the hepcidin-ferroportin axis, erythroid iron regulation, standardized hepcidin assays, and next-generation sequencing have substantially refined diagnosis, while expert guidance for iron-refractory iron deficiency anemia (IRIDA) has refined management, and hepcidin-targeted therapies in early development signal a shift towards mechanism-based treatment, though their role in IRIDA remains investigational. This review provides an updated, clinically oriented framework for inherited microcytic anemias caused by defects in systemic iron homeostasis, cellular iron transport, mitochondrial iron utilization, and heme biosynthesis. We propose a contemporary diagnostic algorithm integrating clinical features, iron biomarkers, hepcidin assessment, and molecular testing, and review current and emerging therapeutic strategies. Early recognition enables accurate diagnosis, avoids inappropriate investigations and treatment, facilitates genetic counselling, and helps prevent irreversible organ damage, particularly in iron-overload disorders.