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Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia

Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assesse...

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Autores principales: van der Staaij, Hilde, Donker, Albertine E., Bakkeren, Dirk L., Salemans, Jan M. J. I., Mignot-Evers, Lisette A. A., Bongers, Marlies Y., Dieleman, Jeanne P., Galesloot, Tessel E., Laarakkers, Coby M., Klaver, Siem M., Swinkels, Dorine W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836508/
https://www.ncbi.nlm.nih.gov/pubmed/35163840
http://dx.doi.org/10.3390/ijms23031917
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author van der Staaij, Hilde
Donker, Albertine E.
Bakkeren, Dirk L.
Salemans, Jan M. J. I.
Mignot-Evers, Lisette A. A.
Bongers, Marlies Y.
Dieleman, Jeanne P.
Galesloot, Tessel E.
Laarakkers, Coby M.
Klaver, Siem M.
Swinkels, Dorine W.
author_facet van der Staaij, Hilde
Donker, Albertine E.
Bakkeren, Dirk L.
Salemans, Jan M. J. I.
Mignot-Evers, Lisette A. A.
Bongers, Marlies Y.
Dieleman, Jeanne P.
Galesloot, Tessel E.
Laarakkers, Coby M.
Klaver, Siem M.
Swinkels, Dorine W.
author_sort van der Staaij, Hilde
collection PubMed
description Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes. Plasma hepcidin-25 levels were measured by standardized isotope dilution mass spectrometry. IDA controls had not received iron therapy in the last 3 months and C-reactive protein levels were <10.0 mg/L. IRIDA patients had significantly lower TSAT/hepcidin ratios compared to IDA controls, median 0.6%/nM (interquartile range, IQR, 0.4–1.1%/nM) and 16.7%/nM (IQR, 12.0–24.0%/nM), respectively. The area under the curve for the TSAT/hepcidin ratio was 1.000 with 100% sensitivity and specificity (95% confidence intervals 84–100% and 91–100%, respectively) at an optimal cut-off point of 5.6%/nM. The TSAT/hepcidin ratio shows excellent performance in discriminating IRIDA from TMPRSS6-unrelated IDA early in the diagnostic work-up of IDA provided that recent iron therapy and moderate-to-severe inflammation are absent. These observations warrant further exploration in a broader IDA population.
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spelling pubmed-88365082022-02-12 Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia van der Staaij, Hilde Donker, Albertine E. Bakkeren, Dirk L. Salemans, Jan M. J. I. Mignot-Evers, Lisette A. A. Bongers, Marlies Y. Dieleman, Jeanne P. Galesloot, Tessel E. Laarakkers, Coby M. Klaver, Siem M. Swinkels, Dorine W. Int J Mol Sci Article Pathogenic TMPRSS6 variants impairing matriptase-2 function result in inappropriately high hepcidin levels relative to body iron status, leading to iron refractory iron deficiency anemia (IRIDA). As diagnosing IRIDA can be challenging due to its genotypical and phenotypical heterogeneity, we assessed the transferrin saturation (TSAT)/hepcidin ratio to distinguish IRIDA from multi-causal iron deficiency anemia (IDA). We included 20 IRIDA patients from a registry for rare inherited iron disorders and then enrolled 39 controls with IDA due to other causes. Plasma hepcidin-25 levels were measured by standardized isotope dilution mass spectrometry. IDA controls had not received iron therapy in the last 3 months and C-reactive protein levels were <10.0 mg/L. IRIDA patients had significantly lower TSAT/hepcidin ratios compared to IDA controls, median 0.6%/nM (interquartile range, IQR, 0.4–1.1%/nM) and 16.7%/nM (IQR, 12.0–24.0%/nM), respectively. The area under the curve for the TSAT/hepcidin ratio was 1.000 with 100% sensitivity and specificity (95% confidence intervals 84–100% and 91–100%, respectively) at an optimal cut-off point of 5.6%/nM. The TSAT/hepcidin ratio shows excellent performance in discriminating IRIDA from TMPRSS6-unrelated IDA early in the diagnostic work-up of IDA provided that recent iron therapy and moderate-to-severe inflammation are absent. These observations warrant further exploration in a broader IDA population. MDPI 2022-02-08 /pmc/articles/PMC8836508/ /pubmed/35163840 http://dx.doi.org/10.3390/ijms23031917 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
van der Staaij, Hilde
Donker, Albertine E.
Bakkeren, Dirk L.
Salemans, Jan M. J. I.
Mignot-Evers, Lisette A. A.
Bongers, Marlies Y.
Dieleman, Jeanne P.
Galesloot, Tessel E.
Laarakkers, Coby M.
Klaver, Siem M.
Swinkels, Dorine W.
Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
title Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
title_full Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
title_fullStr Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
title_full_unstemmed Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
title_short Transferrin Saturation/Hepcidin Ratio Discriminates TMPRSS6-Related Iron Refractory Iron Deficiency Anemia from Patients with Multi-Causal Iron Deficiency Anemia
title_sort transferrin saturation/hepcidin ratio discriminates tmprss6-related iron refractory iron deficiency anemia from patients with multi-causal iron deficiency anemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836508/
https://www.ncbi.nlm.nih.gov/pubmed/35163840
http://dx.doi.org/10.3390/ijms23031917
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