title: Iron disorders of genetic origin: a changing world.
abstract: Iron disorders of genetic origin are mainly composed of iron overload diseases, the most frequent being HFE-related hemochromatosis. Hepcidin deficiency underlies iron overload in HFE-hemochromatosis as well as in several other genetic iron excess disorders, such as hemojuvelin or hepcidin-related hemochromatosis and transferrin receptor 2-related hemochromatosis. Deficiency of ferroportin, the only known cellular protein iron exporter, produces iron overload in the typical form of ferroportin disease. By contrast, genetically enhanced hepcidin production, as observed in matriptase-2 deficiency, generates iron-refractory iron deficiency anemia. Diagnosis of these iron storage disorders is usually established noninvasively through combined biochemical, imaging and genetic approaches. Moreover, improved knowledge of the molecular mechanisms accounting for the variations of iron stores opens the way of novel therapeutic approaches aiming to restore normal iron homeostasis. In this review, we will summarize recent findings about these various genetic entities that have been identified owing to an exemplary interplay between clinicians and basic scientists.
authors.affiliation: Liver Disease Department, National Center of Reference for Rare Iron Overload Diseases of Genetic Origin, INSERM, UMR 991, Liver Metabolisms and Cancer, University of Rennes 1, CHU Pontchaillou, Rennes, France. pierre.brissot@univ-rennes1.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Brissot
authors.forename: Edouard
authors.initials: E
authors.lastname: Bardou-Jacquet
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Jouanolle
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics*; D058851:GPI-Linked Proteins / Q000235:genetics*; D005799:Genes, Dominant; D005808:Genes, Recessive; D005820:Genetic Testing; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D009154:Mutation; D051381:Rats; D011990:Receptors, Transferrin; D012697:Serine Endopeptidases / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D058851:GPI-Linked Proteins; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D007501:Iron; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D012697:Serine Endopeptidases; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C578702:HAMP protein, human; C103673:HFE protein, human; C481006:HJV protein, human; C579599:Hamp protein, mouse; C578703:Hamp protein, rat; C503640:TFR2 protein, human; C467801:matriptase 2