Serum Erythroferrone Level and Its Relation to Iron Overload in Patients with Βeta-Thalassemia

Abstract: BACKGROUND: Iron overload is unavoidable in both transfusion-dependent and non-transfusion-dependent β-thalassemic patients and may lead to significant complications. Hepcidin regulation is influenced by erythroferrone (ERFE), a recently identified erythroid regulator of iron homeostasis. AIMS AND OBJECTIVES: This study aimed to investigate circulating erythroferrone levels and their relationship with serum hepcidin levels, as well as laboratory and imaging markers of iron overload in children with β-thalassemia. MATERIALS AND METHODS: This cross-sectional diagnostic study included 67 β-thalassemic children attending the Hematology Clinic at Alexandria University Children’s Hospital and 20 age-matched healthy controls. Serum ERFE and hepcidin levels were measured using ELISA. Iron overload was assessed using serum ferritin and MRI-based liver and cardiac iron measurements. RESULTS: The median ERFE level was 287.26 ng/L in the transfusion-dependent β-thalassemia group and 283.96 ng/L in the non–transfusion-dependent group, both significantly higher than the reference group (100.53 ng/L). ERFE demonstrated a strong inverse correlation with serum hepcidin levels in both thalassemia groups, while no consistent associations were observed with ferritin or MRI-derived iron parameters. CONCLUSIONS: ERFE levels are elevated in both transfusion-dependent and non–transfusion-dependent β-thalassemia and are inversely associated with circulating hepcidin. These findings support the role of ERFE as a marker of erythropoietic activity rather than tissue iron burden in pediatric β-thalassemia.