Burosumab treatment for FGF23-related hypophosphatemia in a two-year-old girl with McCune-Albright syndrome.

McCune-Albright syndrome (MAS) is a rare mosaic disorder caused by a gain-of-function pathogenic GNAS variant that triggers endocrine and skeletal manifestations, including fibrous dysplasia (FD) and FGF23-related hypophosphatemia. Conventional treatments (e.g., phosphate supplementation, vitamin D analogs) have shown limited efficacy against MAS. Burosumab, a monoclonal FGF23-targeting antibody, has recently been reported as a potential treatment. We report the case of a 2-yr-old girl with MAS complicated by hyperthyroidism, gonadotropin-independent precocious puberty, excess GH, Cushing syndrome, FD, and FGF23-related hypophosphatemia. Genetic testing confirmed a pathogenic GNAS variant (p.Arg201Cys). By the age of 16 mo, she experienced > 7 fractures. Burosumab (1.0 mg/kg bi-weekly) was administered at age 2 yr and 3 mo. Her serum phosphate levels normalized, tubular maximum reabsorption of phosphate-to-glomerular filtration rate ratio improved, bone pain resolved, and she experienced no further fractures since 2 yr and 7 mo, as of age 4 yr and 6 mo. To our knowledge, our patient is the youngest MAS patient treated with burosumab and the second reported case to receive burosumab among patients with genetically confirmed MAS. Burosumab improved biochemical abnormalities related to excess FGF23 and reduced fracture occurrence in our patient, supporting its efficacy in treating FGF23-related hypophosphatemia due to MAS.