Skip to main content

Panel Discussion: Some Aspects of the Management of Patients with X-Linked Hypophosphataemic Rickets

A Correction to this article was published on 17 June 2020

A Correction to this article was published on 23 May 2020

This article has been updated

Abstract

X-linked hypophosphataemia (XLH) rickets is a rare disease frequently misdiagnosed and mismanaged. Despite having clinical guidelines that offers some therapeutic recommendations based on the clinical experience of experts, physicians still have questions about some important aspects of the diagnosis and treatment of XLH, such as when the disease should be suspected, who should be in charge of the diagnosis, what should be done once the disease is diagnosed, or what therapeutic options are currently available. The objective of this paper is to answer some of the more frequent questions related to the management of patients with XLH by a group of experts participating in a scientific conference on XLH held in Madrid.

This is a preview of subscription content, access via your institution.

Change history

  • 23 May 2020

    In the original article, third author name has been published incorrectly.

  • 17 June 2020

    In the original article, there is an error in age related reference.

References

  1. Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381–8.

    Article  Google Scholar 

  2. Capelli S, Donghi V, Maruca K, et al. Clinical and molecular heterogeneity in a large series of patients with hypophosphatemic rickets. Bone. 2015;79:143–9.

    CAS  Article  Google Scholar 

  3. Shopfner CE, Coin CG. Genu varus and valgus in children. Radiology. 1969;92(4):723–32.

    CAS  Article  Google Scholar 

  4. Heath CH, Staheli LT. Normal limits of knee angle in white children - genu varum and genu valgum. J Pediatr Orthop. 1993;13(2):259–62.

    CAS  PubMed  Google Scholar 

  5. Vega RA, Opalak C, Harshbarger RJ, et al. Hypophosphatemic rickets and craniosynostosis: a multicenter case series. J Neurosurg Pediatr. 2016;17(6):694–700.

    Article  Google Scholar 

  6. del Pino M, Viterbo G, Fano V. Manejo de niños con raquitismo hipofosfatémico familiar 2017 [January 16]. http://www.garrahan.gov.ar/images/intranet/guias_atencion/GAP_2017_-_MANEJO_RAQUITISMO.pdf. Accessed 10 Feb 2019.

  7. Bistarakis L, Voskaki I, Lambadaridis J, Sereti H, Sbyrakis S. Renal handling of phosphate in the first six months of life. Arch Dis Child. 1986;61(7):677–81.

    CAS  Article  Google Scholar 

  8. Shaw NJ, Wheeldon J, Brocklebank JT. Indices of intact serum parathyroid hormone and renal excretion of calcium, phosphate, and magnesium. Arch Dis Child. 1990;65(11):1208–11.

    CAS  Article  Google Scholar 

  9. Lambert AS, Linglart A. Hypocalcaemic and hypophosphatemic rickets. Best Pract Res Clin Endocrinol Metab. 2018;32(4):455–76.

    CAS  Article  Google Scholar 

  10. Schaumberger E, Hohenauer L, Sommer R. Early diagnosis and early treatment of hypophosphatemic vitamin D-resistant rickets. Klin Padiatr. 1986;198(1):44–8.

    CAS  Article  Google Scholar 

  11. Carpenter TO, Shaw NJ, Portale AA, Ward LM, Abrams SA, Pettifor JM. Rickets. Nat Rev Dis Primers. 2017;3:17101.

    Article  Google Scholar 

  12. Elder CJ, Bishop NJ. Rickets. Lancet. 2014;383(9929):1665–76.

    Article  Google Scholar 

  13. Goldsweig BK, Carpenter TO. Hypophosphatemic rickets: lessons from disrupted FGF23 control of phosphorus homeostasis. Curr Osteoporos Rep. 2015;13(2):88–97.

    Article  Google Scholar 

  14. Payne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation. Ann Clin Biochem. 1998;35(Pt 2):201–6.

    CAS  Article  Google Scholar 

  15. Walton RJ, Bijvoet OL. Nomogram for derivation of renal threshold phosphate concentration. Lancet. 1975;2(7929):309–10.

    CAS  Article  Google Scholar 

  16. Phelps K, Mason DL. Evidence that TmP/GFR can be estimated with the Walton-Bijvoet nomogram in chronic kidney disease. Clin Nephrol. 2017;88(1):19–26.

    Article  Google Scholar 

  17. Lyseng-Williamson KA. Burosumab in X-linked hypophosphatemia: a profile of its use in the USA. Drugs Ther Perspect. 2018;34(11):497–506.

    Article  Google Scholar 

  18. Imel EA, Econs MJ. Fibroblast growth factor 23: roles in health and disease. J Am Soc Nephrol. 2005;16(9):2565–75.

    CAS  Article  Google Scholar 

  19. Liu S, Quarles LD. How fibroblast growth factor 23 works. J Am Soc Nephrol. 2007;18(6):1637–47.

    CAS  Article  Google Scholar 

  20. Jonsson KB, Zahradnik R, Larsson T, et al. Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med. 2003;348(17):1656–63.

    CAS  Article  Google Scholar 

  21. Riminucci M, Collins MT, Fedarko NS, et al. FGF-23 in fibrous dysplasia of bone and its relationship to renal phosphate wasting. J Clin Invest. 2003;112(5):683–92.

    CAS  Article  Google Scholar 

  22. Igaki JM, Yamada M, Yamazaki Y, et al. High iFGF23 level despite hypophosphatemia is one of the clinical indicators to make diagnosis of XLH. Endocr J. 2011;58(8):647–55.

    CAS  Article  Google Scholar 

  23. Imel EA, DiMeglio LA, Hui SL, Carpenter TO, Econs MJ. Treatment of X-linked hypophosphatemia with calcitriol and phosphate increases circulating fibroblast growth factor 23 concentrations. J Clin Endocrinol Metab. 2010;95(4):1846–50.

    CAS  Article  Google Scholar 

  24. Ruppe MD, Zhang X, Imel EA, et al. Effect of four monthly doses of a human monoclonal anti-FGF23 antibody (KRN23) on quality of life in X-linked hypophosphatemia. Bone Rep. 2016;5:158–62.

    Article  Google Scholar 

  25. Sullivan R, Abraham A, Simpson C, et al. Three-month randomized clinical trial of nasal calcitonin in adults with X-linked hypophosphatemia. Calcif Tissue Int. 2018;102(6):666–70.

    CAS  Article  Google Scholar 

  26. Carpenter TO, Imel EA, Ruppe MD, et al. Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. J Clin Invest. 2014;124(4):1587–97.

    CAS  Article  Google Scholar 

  27. Product information Phosphate Sandoz®. https://www.medicines.org.uk/emc/product/958/smpc. Accessed 10 Feb 2019.

  28. Product information Fosfato NM®. http://cima.aemps.es/cima/pdfs/es/ft/81120/81120_ft.pdf. Accessed 10 Feb 2019.

  29. Imel EA, White KE. Pharmacological management of X-linked hypophosphataemia. Br J Clin Pharmacol. 2019;85(6):1188–98.

    Article  Google Scholar 

Download references

Acknowledgements

This supplement has been funded by Kyowa Kirin.

Funding

Kyowa Kirin organized the scientific meeting and contributed to the financing of the publication of the opinion of the speakers presented at that meeting (Madrid, November 2018).

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Medical Writing, Editorial, and Other Assistance

The authors would like to thank Fernando Sánchez Barbero, PhD for providing medical writing assistance on behalf of Springer Healthcare. Kyowa Kirin funded the writing assistance. Ruth Blaikie provided the copy editing of this manuscript.

Disclosures

Josep-Vicent Torregrosa, Jaime Sánchez del Pozo and María Isabel Luis Yanes declare no conflict of interest for the publication of this manuscript. Manuel Muñoz Torres has participated as a speaker and in clinical studies sponsored by Kyowa Kirin.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to José-Vicente Torregrosa.

Additional information

Enhanced Digital Features

To view enhanced digital features for this article go to https://doi.org/10.6084/m9.figshare.11365145.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Torregrosa, JV., Sánchez del Pozo, J., Luiz Yanes, M.I. et al. Panel Discussion: Some Aspects of the Management of Patients with X-Linked Hypophosphataemic Rickets. Adv Ther 37 (Suppl 2), 121–126 (2020). https://doi.org/10.1007/s12325-019-01208-w

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-019-01208-w

Keywords

  • Burosumab
  • Diagnosis
  • FGF23
  • Multidisciplinary
  • Orthopaedics
  • Paediatrician
  • Phosphaturia