Outcome of adult patients with X-linked hypophosphatemia caused by PHEX gene mutations

J Inherit Metab Dis. 2018 Sep;41(5):865-876. doi: 10.1007/s10545-018-0147-6. Epub 2018 Feb 19.

Abstract

X-linked hypophosphatemia (XLH) is the most common monogenic disorder causing hypophosphatemia. This case-note review documents the clinical features and the complications of treatment in 59 adults (19 male, 40 female) with XLH. XLH is associated with a large number of private mutations; 37 different mutations in the PHEX gene were identified in this cohort, 14 of which have not been previously reported. Orthopaedic involvement requiring surgical intervention (osteotomy) was frequent. Joint replacement and decompressive laminectomy were observed in those older than 40 years. Dental disease (63%), nephrocalcinosis (42%), and hearing impairment (14%) were also common. The rarity of the disease and the large number of variants make it difficult to discern specific genotype-phenotype relationships. A new treatment, an anti-FGF23 antibody, that may affect the natural history of the disease is currently being investigated in clinical trials.

Keywords: Dental abcess; Enthesopathy; Nephrocalcinosis; Osteotomy; PHEX; Phosphate regulating endopeptidase homologue; X-linked hypophosphatemia; XLH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Familial Hypophosphatemic Rickets / genetics*
  • Familial Hypophosphatemic Rickets / physiopathology
  • Familial Hypophosphatemic Rickets / therapy*
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / antagonists & inhibitors
  • Fibroblast Growth Factors / immunology
  • Genetic Association Studies
  • Genetic Diseases, X-Linked*
  • Hearing Loss / etiology
  • Humans
  • Laminectomy
  • Male
  • Middle Aged
  • Mutation*
  • Nephrocalcinosis / etiology
  • Osteotomy
  • PHEX Phosphate Regulating Neutral Endopeptidase / genetics*
  • Randomized Controlled Trials as Topic
  • Stomatognathic Diseases / etiology
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • FGF23 protein, human
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • PHEX Phosphate Regulating Neutral Endopeptidase
  • PHEX protein, human