Clinical Diagnosis, Genetic Background and Treatment of Vitamin-D Resistant Hypophosphatemic Ricket

Abstract

X-linked hypophosphatemia (XLH) is the most common heritable form of rickets. It involves loss-of-function mutations in the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene, which give rise to the increase of fibroblast growth factor 23 (FGF23). Excess FGF23 reduces renal phosphate reabsorption, hence hypophosphatemia, and consequentially diminishes the synthesis of active vitamin D. Treatment includes conventional therapy of phosphate and active vitamin D, together with correction of bone deformities and monitoring treatment-related side effects. Burosumab, a recombinant monoclonal antibody directed at FGF23, is a first-line treatment option for XLH.