X-Linked Hypophosphatemia Management in Children: An International Working Group Clinical Practice Guideline

Dalal S. Ali, Division of Endocrinology and Metabolism, McMaster University, Canada.
Thomas O. Carpenter, Departments of Pediatrics (Endocrinology), and Orthopaedics and Rehabilitation, Yale University School of Medicine, New Haven, CT, USA.
Erik A. Imel, Department of Medicine and Pediatrics, Endocrinology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Leanne M. Ward, Children's Hospital of Eastern Ontario, Department of Pediatrics, University of Ottawa, Ottawa, Ontario, Canada.
Natasha M. Appelman-Dijkstra, Department of Internal Medicine, Division of Endocrinology, Center for Bone Quality, Leiden University Medical Center, Leiden, the Netherlands.
Catherine Chaussain, Faculty of Dentistry, Université Paris Cité and APHP, Paris, France.
Suzanne M. de Beur, University of Virginia School of Medicine, Charlottesville, VA, USA.
Pablo Florenzano, Department of Endocrinology, School of Medicine Pontificia Universidad Católica de Chile.
Hajar Abu Alrob, Department of Health Research Methods, Evidence, and Impact at McMaster University.
Rana Aldabagh, Faculty of Dentistry, University of Toronto, Toronto, Canada.
R Todd Alexander, Faculty of Medicine & Dentistry, The University of Alberta, Edmonton, AB, Canada.
Farah Alsarraf, Division of Endocrinology and Metabolism, McMaster University, Canada.
Signe Sparre Beck-Nielsen, Centre for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark and Department for Clinical Research, Aarhus University, Aarhus, Denmark.
Martin Biosse-Duplan, Faculty of Dentistry, Université Paris Cité, Paris, France; Institut Imagine, INSERM 1163, Paris, France; APHP, Paris, France.
Rachel K. Crowley, Rare Disease Clinical Trial Network, University College Dublin, Ireland.
Karel Dandurand, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Guido Filler, Department of Pediatrics, Western University, London, Ontario, Canada.
Lisa Friedlander, Faculty of Dentistry, Université Paris Cité and APHP, Paris, France.
Seiji Fukumoto, Tamaki-Aozora Hospital, Japan.
Claudia Gagnon, Department of Medicine, Université Laval, Quebec City, Canada; CHU de Québec-Université Laval Research Centre, Quebec City, Canada.
Paul Goodyer, Research Institute of the McGill University Health Centre, Montreal, Canada.
Corinna Grasemann, Department of Pediatrics, Division of Rare Diseases, Katholisches Klinikum Bochum and Ruhr-University Bochum, Bochum, Germany.
Chelsey Grimbly, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Salma Hussein, Division of Endocrinology and Metabolism, McMaster University, Canada.
Muhammad K. Javaid, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Sarah Khan, University of Toronto; Bone research and Education Centre, ON, Canada.
Aneal Khan, M.A.G.I.C. Clinic (Metabolics and Genetics in Canada), Calgary, AB, Canada.
Anna Lehman, University of British Columbia; Adult Metabolic Diseases Clinic, Vancouver, BC, Canada.
Willem F. Lems, Department of Rheumatology, Amsterdam UMC, the Netherlands.
E Michael Lewiecki, New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA.
Ciara McDonnell, Department of Paediatric Endocrinology & Diabetes, Children's Health Ireland, Dublin, Ireland.
Reza D. Mirza, Department of Health Research Methods, Evidence, and Impact at McMaster University.

Document Type

Journal Article

Publication Date

2-17-2025

Journal

The Journal of clinical endocrinology and metabolism

DOI

10.1210/clinem/dgaf093

Keywords

X-linked hypophosphatemia (XLH); children; clinical practice guidelines; consensus; pediatrics; rickets

Abstract

BACKGROUND: An International Working Group (IWG) developed new guidelines on the diagnosis, evaluation, management, and monitoring of X-linked hypophosphatemia (XLH) in children. Over the past 5 years, important advances have occurred in our understanding of the presentation, complications and treatment of XLH. METHODS: A group of 50 international experts in XLH from Canada, the United States, Europe, Asia and South America, along with methodology experts and patient partners, held 18 teleconference meetings in 2023-2024. These meetings addressed key issues regarding diagnosing, evaluating, managing, and monitoring XLH in children. Two systematic reviews were conducted to examine the impact of burosumab compared to conventional therapy (phosphate salts and active vitamin D) or no therapy, and to assess the impact of conventional therapy versus no therapy on patient-important outcomes. The certainty of evidence was evaluated using the GRADE methodology. Additionally, narrative reviews were completed on XLH diagnosis and the role of genetic testing, and an expert clinical practice survey informed the monitoring recommendations. OUTCOMES: An approach to establishing the diagnosis of XLH is presented. GRADEd recommendations were developed on treatment strategies for XLH in children. Monitoring recommendations, GRADEd as weak with very low certainty, were based on clinical practice survey of the IWG experts. The guidelines also addressed dental complications and proposed potential strategies to mitigate them. CONCLUSION: These clinical practice guidelines provide an update of the current evidence on the diagnosis and management of XLH and provide a comprehensive guidance for multidisciplinary healthcare professionals involved in the care of children with XLH.

Department

Orthopaedic Surgery

Link to Full Text

Share

COinS