Hereditary hypotransferrinemia can lead to elevated transferrin saturation and, when associated to HFE or HAMP mutations, to iron overload

Marie-Pascale Beaumont-Epinette; Jean-Bernard Delobel; Martine Ropert; Yves Deugnier; Olivier Loréal; Anne-Marie Jouanolle; Pierre Brissot; Edouard Bardou-Jacquet

doi:10.1016/j.bcmd.2014.11.020

Hereditary hypotransferrinemia can lead to elevated transferrin saturation and, when associated to HFE or HAMP mutations, to iron overload

Blood Cells Mol Dis. 2015 Feb;54(2):151-4. doi: 10.1016/j.bcmd.2014.11.020. Epub 2014 Nov 26.

Authors

Marie-Pascale Beaumont-Epinette¹, Jean-Bernard Delobel², Martine Ropert³, Yves Deugnier⁴, Olivier Loréal⁵, Anne-Marie Jouanolle¹, Pierre Brissot⁶, Edouard Bardou-Jacquet⁶

Affiliations

¹ 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.
² CHU Rennes, Liver Disease Department, F-35033 Rennes, France.
³ 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.
⁴ 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.
⁵ 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.
⁶ 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.

PMID: 25486930
DOI: 10.1016/j.bcmd.2014.11.020

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.

Keywords: Hemochromatosis; Iron overload; Tranferrin; Transferrin saturation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
DNA Mutational Analysis
Female
Gene Expression
Genotype
Hemochromatosis Protein
Hepcidins / genetics*
Hepcidins / metabolism
Heterozygote
Histocompatibility Antigens Class I / genetics*
Histocompatibility Antigens Class I / metabolism
Humans
Iron / metabolism*
Iron Overload / blood
Iron Overload / etiology
Iron Overload / genetics*
Iron Overload / pathology
Male
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Metal Metabolism, Inborn Errors / blood
Metal Metabolism, Inborn Errors / complications
Metal Metabolism, Inborn Errors / genetics*
Metal Metabolism, Inborn Errors / pathology
Middle Aged
Mutation*
Pedigree
Transferrin / deficiency*
Transferrin / genetics*
Transferrin / metabolism

Substances

HAMP protein, human
HFE protein, human
Hemochromatosis Protein
Hepcidins
Histocompatibility Antigens Class I
Membrane Proteins
Transferrin
Iron

Supplementary concepts

Congenital atransferrinemia