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Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia

Autosomal dominant hypophosphatemia (ADH) causes rickets, osteomalacia, and taurodontism due to heterozygous mutations in FGF23, which inhibit the inactivation (cleavage) of the encoded protein, the hormone fibroblast growth factor 23 (FGF23). Iron deficiency increases FGF23 mRNA expression and rece...

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Autores principales: Högler, Wolfgang, Kapelari, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027502/
https://www.ncbi.nlm.nih.gov/pubmed/31834957
http://dx.doi.org/10.1002/jbmr.3941
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author Högler, Wolfgang
Kapelari, Klaus
author_facet Högler, Wolfgang
Kapelari, Klaus
author_sort Högler, Wolfgang
collection PubMed
description Autosomal dominant hypophosphatemia (ADH) causes rickets, osteomalacia, and taurodontism due to heterozygous mutations in FGF23, which inhibit the inactivation (cleavage) of the encoded protein, the hormone fibroblast growth factor 23 (FGF23). Iron deficiency increases FGF23 mRNA expression and recent evidence suggests that the recurrent, late‐onset, or waxing‐waning hypophosphatemic phenotype may be linked to synchronous variations in iron status. The fact that most adult symptomatic ADH patients are females during reproductive age supports the notion of a gene‐environmental interaction. Practically all symptomatic hypophosphatemic patients described in the recent literature were also iron deficient (with/without anemia) at presentation, when measured. Given its interaction with FGF23, correcting iron deficiency should therefore also correct FGF23 excess. Following the original report of successful phenotype reversal in an iron‐deficient ADH child using oral iron supplementation in 2015, more evidence has emerged that supports the use of the element iron to restore homoeostasis of the element phosphorus (in addition to its own). We put into perspective the recent evidence and add 14 years observational data on the original case that demonstrates the correlation of serum phosphorus and renal tubular phosphate reabsorption in mass per unit volume of glomerular filtrate (TmP/GFR) with serum ferritin. Presentation and relapse of ADH, 12 years apart, occurred during iron deficiency, and the onset of menstrual periods was associated with relapse. Here we propose management guidance for patients affected by ADH throughout the lifespan based on iron stores. Because ferritin correlates best with hypophosphatemia historically, and in long‐term observation of the originally treated case, it should be used as the monitoring tool and kept in the normal range. Women with ADH who are of reproductive age and other risk groups require supplementation with oral iron using WHO guidelines. Treatment of this form of FGF23 excess may not require phosphate and active vitamin D, or burosumab. © 2020 American Society for Bone and Mineral Research
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spelling pubmed-70275022020-02-24 Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia Högler, Wolfgang Kapelari, Klaus J Bone Miner Res Perspective Autosomal dominant hypophosphatemia (ADH) causes rickets, osteomalacia, and taurodontism due to heterozygous mutations in FGF23, which inhibit the inactivation (cleavage) of the encoded protein, the hormone fibroblast growth factor 23 (FGF23). Iron deficiency increases FGF23 mRNA expression and recent evidence suggests that the recurrent, late‐onset, or waxing‐waning hypophosphatemic phenotype may be linked to synchronous variations in iron status. The fact that most adult symptomatic ADH patients are females during reproductive age supports the notion of a gene‐environmental interaction. Practically all symptomatic hypophosphatemic patients described in the recent literature were also iron deficient (with/without anemia) at presentation, when measured. Given its interaction with FGF23, correcting iron deficiency should therefore also correct FGF23 excess. Following the original report of successful phenotype reversal in an iron‐deficient ADH child using oral iron supplementation in 2015, more evidence has emerged that supports the use of the element iron to restore homoeostasis of the element phosphorus (in addition to its own). We put into perspective the recent evidence and add 14 years observational data on the original case that demonstrates the correlation of serum phosphorus and renal tubular phosphate reabsorption in mass per unit volume of glomerular filtrate (TmP/GFR) with serum ferritin. Presentation and relapse of ADH, 12 years apart, occurred during iron deficiency, and the onset of menstrual periods was associated with relapse. Here we propose management guidance for patients affected by ADH throughout the lifespan based on iron stores. Because ferritin correlates best with hypophosphatemia historically, and in long‐term observation of the originally treated case, it should be used as the monitoring tool and kept in the normal range. Women with ADH who are of reproductive age and other risk groups require supplementation with oral iron using WHO guidelines. Treatment of this form of FGF23 excess may not require phosphate and active vitamin D, or burosumab. © 2020 American Society for Bone and Mineral Research John Wiley & Sons, Inc. 2019-12-31 2020-02 /pmc/articles/PMC7027502/ /pubmed/31834957 http://dx.doi.org/10.1002/jbmr.3941 Text en © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Perspective
Högler, Wolfgang
Kapelari, Klaus
Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia
title Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia
title_full Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia
title_fullStr Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia
title_full_unstemmed Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia
title_short Oral Iron for Prevention and Treatment of Rickets and Osteomalacia in Autosomal Dominant Hypophosphatemia
title_sort oral iron for prevention and treatment of rickets and osteomalacia in autosomal dominant hypophosphatemia
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027502/
https://www.ncbi.nlm.nih.gov/pubmed/31834957
http://dx.doi.org/10.1002/jbmr.3941
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