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

Nat Rev Nephrol. 2019 Jul;15(7):435-455. doi: 10.1038/s41581-019-0152-5.


X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care.

Publication types

  • Consensus Development Conference
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Arnold-Chiari Malformation / etiology
  • Biomarkers / blood
  • Bone Density Conservation Agents / therapeutic use
  • Bone and Bones / diagnostic imaging
  • Continuity of Patient Care
  • Craniosynostoses / prevention & control
  • Delphi Technique
  • Dental Care
  • Familial Hypophosphatemic Rickets / diagnosis*
  • Familial Hypophosphatemic Rickets / therapy*
  • Fibroblast Growth Factor-23
  • Growth Hormone / therapeutic use
  • Hearing Loss / etiology
  • Hearing Loss / prevention & control
  • Humans
  • Immunologic Factors / therapeutic use
  • Life Style
  • Mutation
  • Orthopedic Procedures
  • PHEX Phosphate Regulating Neutral Endopeptidase / genetics
  • Phosphates / therapeutic use
  • Physical Therapy Modalities
  • Radiography
  • Vitamin D / therapeutic use


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Bone Density Conservation Agents
  • FGF23 protein, human
  • Immunologic Factors
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factor-23
  • Growth Hormone
  • PHEX Phosphate Regulating Neutral Endopeptidase
  • PHEX protein, human
  • burosumab