The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide review the pathophysiology related pharmacology this condition, primarily focusing on FDA-approved medication burosumab. XLH is renal phosphate wasting disorder caused by loss function mutations in PHEX gene (phosphate-regulating with homologies to endopeptidases X chromosome). Typical biochemical findings include elevated serum levels bioactive/intact fibroblast growth factor 23 (FGF23) which lead (i) low levels, (ii) increased fractional excretion phosphate, (iii) inappropriately or normal 1,25-dihydroxyvitamin D (1,25-vitD). most common form heritable rickets short stature patients due chronic hypophosphatemia. Additionally, experience joint pain osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, hearing loss. Historically, treatment for was limited oral supplementation, active vitamin surgical intervention cases severe bowed legs. In 2018, United States Food Drug Administration (FDA) approved burosumab has demonstrated substantial benefit compared conventional therapy. Burosumab binds circulating intact FGF23 blocks its biological effects target tissues, resulting inorganic (Pi) concentrations conversion inactive 1,25-vitD.