X-linked hypophosphataemic rickets

Abstract

X-linked hypophosphataemic (XLH) rickets is a rare bone disorder caused by an X-linked dominant variant in the phosphate regulating endopeptidase homolog called PHEX, which leads to in an increase fibroblast growth factor-23 (FGF23), and, in turn, excessive renal phosphate wasting. While XLH was primarily thought to be a disease of childhood with short stature, bone pain and fractures, it is becoming increasingly apparent that XLH continues to cause progressive skeletal and non-skeletal complications in adulthood. Adults can present with multiple potential causes for skeletal pain and dysfunction. Careful history and examination are needed to identity the likely culprit pathologies and guide further imaging and treatment, in particular spinal stenosis and Arnold Chiari malformations need to be ruled out. In adults, a low threshold is needed for imaging to exclude pseudofractures, especially of the femur. Management has been transformed by targeted antibody therapy to remove excess FGF23 using burosumab. The effect of burosumab to improve musculoskeletal health highlights the need for close collaboration between different disciplines for the optimal care of adults with XLH.