Current Practices in Monitoring Children and Adults With X-linked Hypophosphatemia: A Global Survey of Expert Experience

Dalal S Ali; Farah Alsarraf; Hajar Abu Alrob; R Todd Alexander; Abdulrahman Almoulia; Natasha M Appelman-Dijkstra; Signe Sparre Beck-Nielsen; Martin Biosse-Duplan; Maria Luisa Brandi; Thomas O Carpenter; Catherine Chaussain; Martine Cohen-Solal; Rachel K Crowley; Karel Dandurand; Pablo Florenzano; Claudia Gagnon; Paul Goodyer; Chelsey Grimbly; Salma Hussein; Erik A Imel; Suzanne M Jan de Beur; Muhammad K Javaid; Anna Lehman; Willem F Lems; E Michael Lewiecki; Ciara McDonnell; Reza D Mirza; Emmett Morgante; Anthony A Portale; Yumie Rhee; Heide Siggelkow; Laura L Tosi; Leanne M Ward; Gordon Guyatt; Aliya A Khan

doi:10.1210/clinem/dgaf180

Current Practices in Monitoring Children and Adults With X-linked Hypophosphatemia: A Global Survey of Expert Experience

J Clin Endocrinol Metab. 2025 Jun 17;110(7):e2347-e2361. doi: 10.1210/clinem/dgaf180.

Authors

Dalal S Ali¹, Farah Alsarraf¹, Hajar Abu Alrob², R Todd Alexander³, Abdulrahman Almoulia¹, Natasha M Appelman-Dijkstra⁴, Signe Sparre Beck-Nielsen^{5

6}, Martin Biosse-Duplan^{7

8

9}, Maria Luisa Brandi¹⁰, Thomas O Carpenter¹¹, Catherine Chaussain^{7

8

9}, Martine Cohen-Solal¹², Rachel K Crowley¹³, Karel Dandurand¹⁴, Pablo Florenzano¹⁵, Claudia Gagnon^{16

17}, Paul Goodyer¹⁸, Chelsey Grimbly^{3

19}, Salma Hussein¹, Erik A Imel²⁰, Suzanne M Jan de Beur²¹, Muhammad K Javaid²², Anna Lehman²³, Willem F Lems²⁴, E Michael Lewiecki²⁵, Ciara McDonnell^{26

27}, Reza D Mirza², Emmett Morgante²⁸, Anthony A Portale²⁹, Yumie Rhee³⁰, Heide Siggelkow^{31

32}, Laura L Tosi³³, Leanne M Ward³⁴, Gordon Guyatt^{2

35

36}, Aliya A Khan¹

Affiliations

¹ Division of Endocrinology and Metabolism, McMaster University, Hamilton, ON L8S 4L8, Canada.
² Department of Health Research Methods, Evidence, and Impact at McMaster University, Hamilton, ON L8S 4L8, Canada.
³ Department of Pediatrics, Faculty of Medicine & Dentistry, The University of Alberta, Edmonton, AB T6G 2R3, Canada.
⁴ Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality, Leiden University Medical Center, 2300 ZA, Leiden, The Netherlands.
⁵ Centre for Rare Diseases, Aarhus University Hospital, Aarhus N 8200, Denmark and Department for Clinical Research, Aarhus University, Aarhus N 8200, Denmark.
⁶ Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark.
⁷ Department of Oral Medicine, Faculty of Dentistry, UMR 1333, Université Paris Cité, 75006 Paris, France.
⁸ Institut Imagine, INSERM 1163, 75015 Paris, France.
⁹ Department of Oral Medicine, APHP, 75006 Paris, France.
¹⁰ Institute of Endocrine and Metabolic Sciences, Vita-Salute San Raffaele University and IRCCS, 20132, Milan, Italy.
¹¹ Departments of Pediatrics (Endocrinology), and Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT 06520, USA.
¹² Department of Rheumatology and Reference Center for Rare Bone Diseases, Hospital Lariboisiere, 75010 Paris, France.
¹³ Rare Disease Clinical Trial Network, University College Dublin, Dublin 4 D04T6F4, Ireland.
¹⁴ Division of Internal Medicine, Endocrinology Division, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
¹⁵ Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile, 8320165 Santiago, Chile.
¹⁶ Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Centre, Québec, QC G1V 4G2, Canada.
¹⁷ Department of Medicine, Université Laval, Québec, QC G1V 0A6, Canada.
¹⁸ Research Institute of the McGill University Health Centre, Montreal, QC H3H 2L9, Canada.
¹⁹ Women and Children's Health Research Institute, Edmonton, AB T6G 1C9, Canada.
²⁰ Department of Medicine and Pediatrics, Endocrinology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
²¹ Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22903, USA.
²² Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7HE, UK.
²³ Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
²⁴ Department of Rheumatology, Amsterdam UMC, Amsterdam 1105 AZ, The Netherlands.
²⁵ New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM 87106, USA.
²⁶ Department of Paediatric Endocrinology & Diabetes, Children's Health Ireland, Dublin D12 N512, Ireland.
²⁷ Department of Paediatrics, School of Medicine, University of Dublin, Trinity College, Dublin D02 PN40, Ireland.
²⁸ Department of Kinesiology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
²⁹ Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94115, USA.
³⁰ Endocrine Research Institute, Department of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
³¹ Department of Trauma, Orthopedics and Reconstructive Surgery, University Medical Center Goettingen, 37075 Goettingen, Germany.
³² MVZ Endokrinologikum Goettingen, 37075 Goettingen, Germany.
³³ Department of Orthopedics, George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
³⁴ Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, ON K1H 8L1, Canada.
³⁵ Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.
³⁶ MAGIC Evidence Ecosystem Foundation, 0456 Oslo, Norway.

Abstract

This report provides recommendations for X-linked hypophosphatemia (XLH) monitoring based on current monitoring practices of experts in the management of XLH in children (<18 years) and adults. We surveyed 43 international experts in XLH to determine their monitoring practices for children and adults with XLH, including pregnant and lactating women. In the initial evaluation of children and adults with XLH, experts consistently obtain a family history of XLH or hypophosphatemia, a history of fractures and dental infections, and assess pain through age-appropriate clinical interviews or caregiver reports. They measure height, weight, and blood pressure and conduct DNA analysis of multiple genes associated with hypophosphatemia including the PHEX gene. For children follow-up, experts arrange follow-up every 3 to 6 months assessing height, weight, and blood pressure and examining for skeletal deformities. Laboratory tests in children include serum phosphorus, corrected total/ionized calcium, alkaline phosphatase, renal function, and PTH and spot morning urine for calcium, creatinine, and phosphorus. During adult follow-up, experts assess patients every 6 to 12 months, with a clinical examination focused on skeletal deformities and joint involvement. The laboratory profile is completed at least once a year. In the presence of bone pain, experts conduct X-rays both in children and adults to evaluate for fractures or joint damage. With respect to nephrocalcinosis, renal ultrasound is suggested on an annual basis or less frequently when monitoring children and adults with XLH. Experts conduct a dental assessment at baseline and then every 6 to 12 months for all patients with XLH. The findings of the survey inform practice for assessing new patients with XLH, monitoring existing patients, and identifying areas for future research. All recommendations based on these practices are weak with very low-quality evidence.

Keywords: GRADEd recommendations; X-linked hypophosphatemia; XLH; expert experience; monitoring practice; survey.

MeSH terms

Adolescent
Adult
Child
Familial Hypophosphatemic Rickets* / diagnosis
Familial Hypophosphatemic Rickets* / genetics
Familial Hypophosphatemic Rickets* / therapy
Female
Humans
Male
Monitoring, Physiologic / methods
Pregnancy