The different genetic forms of hereditary hemochromatosis share as their pathogenic mechanisms the deficiency or dysregulation of the hormone hepcidin or defects involving the hepcidin receptor, ferroportin. 1 Ferroportin is the sole known cellular iron exporter in humans and is present on enterocytes, macrophages, and hepatocytes. 2 Normally, the cell-surface concentration of ferroportin is regulated by its interaction with hepcidin. Hepcidin binding triggers the internalization and degradation of the ferroportin-hepcidin complex, causing a decrease in cellular iron release into plasma. 3

Mutations in the ferroportin (SLC40A1) gene cause iron overload syndromes with autosomal dominant transmission. 4 Ferroportin mutations cause at least 2 distinct phenotypes, depending on the functional alteration of the protein. One subtype of ferroportin mutations, predominantly involving residues located on the putative cytoplasmic side or in transmembrane segments (eg, V162del, D157G, G80S, G490D), results in the loss of iron export function. 5 This leads to increased macrophage iron and elevated serum ferritin, but normal transferrin saturation. This