title: Hereditary hypotransferrinemia can lead to elevated transferrin saturation and, when associated to HFE or HAMP mutations, to iron overload.
abstract: As our understanding of iron metabolism improves through the more accurate description of iron metabolism actors, new causes of iron overload are identified. We, here, report 16 cases of hereditary hypotransferrinemia related to 4 previously undescribed TF (transferrin) mutations (p.Val221Gly, p.Arg609Trp, p.Glu370Lys, p.Tyr533X and p.Cys421Arg). We show that, besides increasing serum transferrin saturation without iron overload, hypotransferrinemia, when associated to mutations in HFE or HAMP or to acquired factors, can lead to clinically relevant iron burden. These cases emphasize the usefulness of serum transferrin determination in the diagnostic evaluation of iron overload and the importance for clinicians to be aware of this syndrome.
authors.affiliation: CHU Rennes, French Reference Center for Rare Iron Overload Diseases of Genetic Origin Rennes, F-35033 Rennes, France; CHU Rennes, Laboratory of Molecular Genetics, F-35033 Rennes, France.
authors.forename: Marie-Pascale
authors.initials: MP
authors.lastname: Beaumont-Epinette
authors.affiliation: CHU Rennes, Liver Disease Department, F-35033 Rennes, France.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Delobel
authors.affiliation: CHU Rennes, French Reference Center for Rare Iron Overload Diseases of Genetic Origin Rennes, F-35033 Rennes, France; CHU Rennes, Laboratory of Biochemistry, F-35033 Rennes, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Ropert
authors.affiliation: CHU Rennes, French Reference Center for Rare Iron Overload Diseases of Genetic Origin Rennes, F-35033 Rennes, France; CHU Rennes, Liver Disease Department, F-35033 Rennes, France; University of Rennes 1, F-35033 Rennes, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Deugnier
authors.affiliation: CHU Rennes, French Reference Center for Rare Iron Overload Diseases of Genetic Origin Rennes, F-35033 Rennes, France; CHU Rennes, Liver Disease Department, F-35033 Rennes, France; INSERM, UMR 991, F-35033 Rennes, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Loréal
authors.affiliation: CHU Rennes, French Reference Center for Rare Iron Overload Diseases of Genetic Origin Rennes, F-35033 Rennes, France; CHU Rennes, Laboratory of Molecular Genetics, F-35033 Rennes, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Jouanolle
authors.affiliation: CHU Rennes, French Reference Center for Rare Iron Overload Diseases of Genetic Origin Rennes, F-35033 Rennes, France; CHU Rennes, Liver Disease Department, F-35033 Rennes, France; INSERM, UMR 991, F-35033 Rennes, France; University of Rennes 1, F-35033 Rennes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Brissot
authors.affiliation: CHU Rennes, French Reference Center for Rare Iron Overload Diseases of Genetic Origin Rennes, F-35033 Rennes, France; CHU Rennes, Liver Disease Department, F-35033 Rennes, France; INSERM, UMR 991, F-35033 Rennes, France; University of Rennes 1, F-35033 Rennes, France.
authors.forename: Edouard
authors.initials: E
authors.lastname: Bardou-Jacquet
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D015870:Gene Expression; D005838:Genotype; D000071020:Hemochromatosis Protein; D064451:Hepcidins / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008664:Metal Metabolism, Inborn Errors / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D014168:Transferrin / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
chemical_list: C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D014168:Transferrin; D007501:Iron
keywords: Hemochromatosis; Iron overload; Tranferrin; Transferrin saturation