Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia.

Catherine Chaussain, Oliver Gardiner, Deborah Eastwood, Kassim M Javaid, Wolfgang Högler, Maria Luisa Brandi, Lothar Seefried, Agnès Linglart, Lars Rejnmark, Peter Kamenický, Elena Levtchenko, Dieter Haffner, Martin Biosse Duplan, Justine Bacchetta, Federico Di Rocco, Detlef Bockenhauer, Gema Ariceta, Francesco Emma, Karine Briot, Dirk Schnabel, Philippe Wicart, Lars Savendahl, Martha Kirchhoff, Pol Harvengt

Journal: Nature reviews. Nephrology 2025;21(5):330-354

PMID: 39814982

Abstract

X-linked hypophosphataemia (XLH) is a rare metabolic bone disorder caused by pathogenic variants in the PHEX gene, which is predominantly expressed in osteoblasts, osteocytes and odontoblasts. XLH is characterized by increased synthesis of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23), which results in renal phosphate wasting with consecutive hypophosphataemia, rickets, osteomalacia, disproportionate short stature, oral manifestations, pseudofractures, craniosynostosis, enthesopathies and osteoarthritis. Patients with XLH should be provided with multidisciplinary care organized by a metabolic bone expert. Historically, these patients were treated with frequent doses of oral phosphate supplements and active vitamin D, which was of limited efficiency and associated with adverse effects. However, the management of XLH has evolved in the past few years owing to the availability of burosumab, a fully humanized monoclonal antibody that neutralizes circulating FGF23. Here, we provide updated clinical practice recommendations for the diagnosis and management of XLH to improve outcomes and quality of life in these patients.

© 2025. Springer Nature Limited.

Address: Department of Paediatric Kidney, Liver, Metabolic and Neurological Diseases, Hannover Medical, School, Hannover, Germany. [email protected].; Center for Congenital Kidney Diseases, Center for Rare Diseases, Hannover Medical School, Hannover, Germany. [email protected].; Division of Nephrology, Children's Hospital Bambino Gesù, IRCCs, Rome, Italy.; Clinical Trial Unit, Orthopedic Institute, Koenig-Ludwig-Haus, University of Würzburg, Würzburg, Germany.; Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria.; Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK.; University College London, Department of Renal Medicine and Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.; Department of Paediatric Nephrology, University Hospitals Leuven, Katholic University of Leuven, Leuven, Belgium.; Paediatric Nephrology Rheumatology and Dermatology Unit, Hospices Civils de Lyon, INSERM1033 Research Unit, Lyon, France.; Department of Orthopaedics, Great Ormond Street Hospital for Children, London, UK.; The Catterall Unit, Royal National Orthopaedic Hospital NHS Trust, Stanmore, UK.; Université Paris Cité, Dental School, Montrouge, France.; APHP, Department of Odontology, Bretonneau Hospital, Paris, France.; APHP, Reference Center for Rare Diseases of Calcium and Phosphate Metabolism, and Filière OSCAR, endo ERN and ERN BOND, Paris, France.; Center for Chronic Sick Children, Paediatric Endocrinology, Charité-University Medicine, Berlin, Germany.; APHP, Reference Center for Rare Diseases of Calcium and Phosphate Metabolism, and Filière OSCAR, endo ERN and ERN BOND, Paris, France.; APHP, Department of Paediatric Orthopedic Surgery, Necker - Enfants Malades University Hospital, Paris, France.; Université Paris Cité, Paris, France.; Department of Paediatric Nephrology, University Hospital Vall d'Hebron, Autonomous University of Barcelona, Barcelona, Spain.; Amsterdam University Medical Centre, Amsterdam, The Netherlands.; International XLH Alliance, London, United Kingdom.; Phosphatdiabetes e.V., German Patient Association for XLH, Lippstadt, Germany.; Paediatric Neurosurgery, Hôpital Femme Mère Enfant, Centre de Référence Craniosténoses, Université de Lyon, INSERM 1033, Lyon, France.; San Raffaele University Hospital, Milan, Italy.; Paediatric Endocrinology Unit, Karolinska University Hospital, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.; APHP, Reference Center for Rare Diseases of Calcium and Phosphate Metabolism, and Filière OSCAR, endo ERN and ERN BOND, Paris, France.; Université Paris Cité, Paris, France.; APHP, Department of Rheumatology, Cochin Hospital, Paris, France.; INSERM UMR-1153, Paris, France.; APHP, Reference Center for Rare Diseases of Calcium and Phosphate Metabolism, and Filière OSCAR, endo ERN and ERN BOND, Paris, France.; Université Paris Saclay, Inserm, AP-HP, Physiologie et Physiopathologie Endocriniennes, Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital Bicêtre Paris Saclay, Le Kremlin Bicêtre, France.; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.; APHP, Reference Center for Rare Diseases of Calcium and Phosphate Metabolism, and Filière OSCAR, endo ERN and ERN BOND, Paris, France.; Université Paris Saclay, Inserm, AP-HP, Physiologie et Physiopathologie Endocriniennes, Service Endocrinologie et diabète de l'enfant, Hôpital Bicêtre Paris Saclay, Le Kremlin-Bicêtre, France.

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