Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features
Iron overloading disorders linked to mutations in ferroportin have diverse phenotypes in vivo, and the effects of mutations on ferroportin in vitro range from loss of function (LOF) to gain of function (GOF) with hepcidin resistance. We reviewed 359 patients with 60 ferroportin variants. Overall, ma...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/12/3/132 |
| id |
doaj-272b1b18cc874fa695a4194c670e34d3 |
|---|---|
| record_format |
Article |
| spelling |
doaj-272b1b18cc874fa695a4194c670e34d32020-11-25T03:59:00ZengMDPI AGPharmaceuticals1424-82472019-09-0112313210.3390/ph12030132ph12030132Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional FeaturesL. Tom Vlasveld0Roel Janssen1Edouard Bardou-Jacquet2Hanka Venselaar3Houda Hamdi-Roze4Hal Drakesmith5Dorine W. Swinkels6Department of Internal Medicine, Haaglanden MC-Bronovo, 2597AX The Hague, The NetherlandsDepartment of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The NetherlandsLiver Diseases Department, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, University Hospital Pontchaillou, 35033 Rennes, FranceCentre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud, University Medical Center, P.O. Box 9191, 6500 HB Nijmegen, The NetherlandsMolecular Genetics Department, French Reference Centre for Rare Iron Overload Diseases of Genetic Origin, University Hospital Pontchaillou, 35033 Rennes, FranceMRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX39DS, UKDepartment of Laboratory Medicine, Translational Metabolic Laboratory, Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The NetherlandsIron overloading disorders linked to mutations in ferroportin have diverse phenotypes in vivo, and the effects of mutations on ferroportin in vitro range from loss of function (LOF) to gain of function (GOF) with hepcidin resistance. We reviewed 359 patients with 60 ferroportin variants. Overall, macrophage iron overload and low/normal transferrin saturation (TSAT) segregated with mutations that caused LOF, while GOF mutations were linked to high TSAT and parenchymal iron accumulation. However, the pathogenicity of individual variants is difficult to establish due to the lack of sufficiently reported data, large inter-assay variability of functional studies, and the uncertainty associated with the performance of available in silico prediction models. Since the phenotypes of hepcidin-resistant GOF variants are indistinguishable from the other types of hereditary hemochromatosis (HH), these variants may be categorized as ferroportin-associated HH, while the entity ferroportin disease may be confined to patients with LOF variants. To further improve the management of ferroportin disease, we advocate for a global registry, with standardized clinical analysis and validation of the functional tests preferably performed in human-derived enterocytic and macrophagic cell lines. Moreover, studies are warranted to unravel the definite structure of ferroportin and the indispensable residues that are essential for functionality.https://www.mdpi.com/1424-8247/12/3/132SLC40A1ferroportiniron overloadnon-HFEferritinhemochromatosis |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
L. Tom Vlasveld Roel Janssen Edouard Bardou-Jacquet Hanka Venselaar Houda Hamdi-Roze Hal Drakesmith Dorine W. Swinkels |
| spellingShingle |
L. Tom Vlasveld Roel Janssen Edouard Bardou-Jacquet Hanka Venselaar Houda Hamdi-Roze Hal Drakesmith Dorine W. Swinkels Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features Pharmaceuticals SLC40A1 ferroportin iron overload non-HFE ferritin hemochromatosis |
| author_facet |
L. Tom Vlasveld Roel Janssen Edouard Bardou-Jacquet Hanka Venselaar Houda Hamdi-Roze Hal Drakesmith Dorine W. Swinkels |
| author_sort |
L. Tom Vlasveld |
| title |
Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features |
| title_short |
Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features |
| title_full |
Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features |
| title_fullStr |
Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features |
| title_full_unstemmed |
Twenty Years of Ferroportin Disease: A Review or An Update of Published Clinical, Biochemical, Molecular, and Functional Features |
| title_sort |
twenty years of ferroportin disease: a review or an update of published clinical, biochemical, molecular, and functional features |
| publisher |
MDPI AG |
| series |
Pharmaceuticals |
| issn |
1424-8247 |
| publishDate |
2019-09-01 |
| description |
Iron overloading disorders linked to mutations in ferroportin have diverse phenotypes in vivo, and the effects of mutations on ferroportin in vitro range from loss of function (LOF) to gain of function (GOF) with hepcidin resistance. We reviewed 359 patients with 60 ferroportin variants. Overall, macrophage iron overload and low/normal transferrin saturation (TSAT) segregated with mutations that caused LOF, while GOF mutations were linked to high TSAT and parenchymal iron accumulation. However, the pathogenicity of individual variants is difficult to establish due to the lack of sufficiently reported data, large inter-assay variability of functional studies, and the uncertainty associated with the performance of available in silico prediction models. Since the phenotypes of hepcidin-resistant GOF variants are indistinguishable from the other types of hereditary hemochromatosis (HH), these variants may be categorized as ferroportin-associated HH, while the entity ferroportin disease may be confined to patients with LOF variants. To further improve the management of ferroportin disease, we advocate for a global registry, with standardized clinical analysis and validation of the functional tests preferably performed in human-derived enterocytic and macrophagic cell lines. Moreover, studies are warranted to unravel the definite structure of ferroportin and the indispensable residues that are essential for functionality. |
| topic |
SLC40A1 ferroportin iron overload non-HFE ferritin hemochromatosis |
| url |
https://www.mdpi.com/1424-8247/12/3/132 |
| work_keys_str_mv |
AT ltomvlasveld twentyyearsofferroportindiseasearevieworanupdateofpublishedclinicalbiochemicalmolecularandfunctionalfeatures AT roeljanssen twentyyearsofferroportindiseasearevieworanupdateofpublishedclinicalbiochemicalmolecularandfunctionalfeatures AT edouardbardoujacquet twentyyearsofferroportindiseasearevieworanupdateofpublishedclinicalbiochemicalmolecularandfunctionalfeatures AT hankavenselaar twentyyearsofferroportindiseasearevieworanupdateofpublishedclinicalbiochemicalmolecularandfunctionalfeatures AT houdahamdiroze twentyyearsofferroportindiseasearevieworanupdateofpublishedclinicalbiochemicalmolecularandfunctionalfeatures AT haldrakesmith twentyyearsofferroportindiseasearevieworanupdateofpublishedclinicalbiochemicalmolecularandfunctionalfeatures AT dorinewswinkels twentyyearsofferroportindiseasearevieworanupdateofpublishedclinicalbiochemicalmolecularandfunctionalfeatures |
| _version_ |
1724456008720318464 |