title: Hepcidin in iron overload disorders.
abstract: Hepcidin is the principal regulator of iron absorption in humans. The peptide inhibits cellular iron efflux by binding to the iron export channel ferroportin and inducing its internalization and degradation. Either hepcidin deficiency or alterations in its target, ferroportin, would be expected to result in dysregulated iron absorption, tissue maldistribution of iron, and iron overload. Indeed, hepcidin deficiency has been reported in hereditary hemochromatosis and attributed to mutations in HFE, transferrin receptor 2, hemojuvelin, and the hepcidin gene itself. We measured urinary hepcidin in patients with other genetic causes of iron overload. Hepcidin was found to be suppressed in patients with thalassemia syndromes and congenital dyserythropoietic anemia type 1 and was undetectable in patients with juvenile hemochromatosis with HAMP mutations. Of interest, urine hepcidin levels were significantly elevated in 2 patients with hemochromatosis type 4. These findings extend the spectrum of iron disorders with hepcidin deficiency and underscore the critical importance of the hepcidin-ferroportin interaction in iron homeostasis.
authors.affiliation: First Department of Medicine, National and Kapodistrian University of Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Papanikolaou
authors.forename: Michalis
authors.initials: M
authors.lastname: Tzilianos
authors.forename: John I
authors.initials: JI
authors.lastname: Christakis
authors.forename: Dionisios
authors.initials: D
authors.lastname: Bogdanos
authors.forename: Konstantina
authors.initials: K
authors.lastname: Tsimirika
authors.forename: Julie
authors.initials: J
authors.lastname: MacFarlane
authors.forename: Y Paul
authors.initials: YP
authors.lastname: Goldberg
authors.forename: Nikos
authors.initials: N
authors.lastname: Sakellaropoulos
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
mesh_terms: D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000652:urine*; D005260:Female; D064451:Hepcidins; D006801:Humans; D019190:Iron Overload / Q000652:urine*; D008297:Male; D008875:Middle Aged
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins