Serum Hepcidin to Prohepcidin Ratio in Children with Iron Deficiency Anemia

Hepcidin is produced in hepatocytes as a precursor form that needs to be converted to a mature hepcidin to be active. In iron deficiency anemia (IDA), the synthesis of hepcidin is inhibited; however, it is not clear how the maturation of hepcidin precursor is affected. To assess the relative maturity of serum hepcidin in the setting of IDA, we compared the ratio of mature hepcidin to prohepcidin in children with different iron statuses.

A total of 51 children (age: 0.6~18.2 yr) with normal renal function and C-reactive protein levels were enrolled. Based on hemoglobin levels and iron status, the subjects were classified as control (n=29), iron deficiency without anemia (n=6), and IDA (n=16). Serum concentrations of hepcidin and prohepcidin were measured by enzyme-linked immunosorbent assays.

Hepcidin was positively correlated with hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, iron, transferrin saturation, and ferritin, and negatively correlated with total iron binding capacity and transferrin. IDA patients had lower levels of prohepcidin [4.7(1.9~21.7) vs 34.6(11.0~140.4) ng/mL, p<0.001] and hepcidin [9.6(3.3~39.5) vs 75.2(19.9~256.4) ng/mL, p<0.001] than control subjects. Hepcidin was strongly correlated with prohepcidin (r=0.991, p<0.001). As compared with control subjects, the hepcidin to prohepcidin ratio was lower in those with IDA (1.89±0.24 vs 2.11±0.18, p=0.009) or low serum ferritin.

These findings suggest that inhibited maturation, as well as inhibited synthesis, may contribute to low hepcidin level in IDA.