IMPE Abstracts

X-linked hypophosphatemia (XLH) caused by phosphate regulating endopeptidase X-linked (PHEX) gene defects is a rare disorder affecting 1 in 20,000 individuals. Loss of PHEX function results in renal phosphate wasting with hypophosphatemia via increased serum FGF23. Clinical features in XLH are growth delay, rickets, limb deformities, and bone pain. Burosumab, a monoclonal antibody against FGF23, had slightly improved height Z-score and radiographical findings in severe XLH patients. However, there are few reports of its use in relatively mild cases. Here we report the effectiveness of burosumab in two siblings with mild XLH. Case 1: 8-month-old, younger sister. The mother had been diagnosed with rickets in childhood and treated with phosphate and active vitamin D. The patient presented growth failure without genu varum. Hypophosphatemia, elevated ALP and FGF23, and inappropriately normal 1,25(OH)2D were detected. Radiographical findings showed Thacher rickets severity total score (RSS) of 6. Therefore, we diagnosed her as XLH. Conventional treatment with phosphate and active vitamin D was administered, which improved XLH findings (RSS = 1). Due to the inconvenience of treatment, the family opted for burosumab at 5 years of age. Burosumab induction with 10 mg / 2 weeks was insufficient to normalize phosphorus levels, resulting in gastrocnemius myalgia pain. The dose-up of burosumab to 20 mg / 2 weeks ameliorated laboratory findings and symptoms. During 1.8 years of burosumab treatment before puberty, height and growth velocity increased (height, -1.30 to -0.64 SDS; growth velocity, +1.46 to +2.65 SDS) with the improvement of X-ray findings (RSS = 0). Case 2: 5-year-old, the older sister of Case 1. She had normal height with genu valgum and complained of leg pain. Based on similar features to Case 1, she was also diagnosed with XLH. Conventional treatment was only enough to improve serum phosphorus levels. During the same period with burosumab in puberty, height and growth velocity increased (growth velocity, -0.01 to +1.29 SDS) with the improvement of X-ray findings (RSS = 0). Even in mild XLH patients, burosumab showed further improvement in laboratory and X-ray findings compared to conventional treatment. Upon transition, all symptoms of XLH after initiating burosumab should be reassessed with suitable serum phosphorus levels. Notably, the burosumab in our cases sustained prepubertal catch-up growth, although height SDS gradually decreases in XLH even after starting conventional treatment early in the disease. Further clinical studies are needed to determine whether burosumab can further improve growth in mild XLH.