Abstract
Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a rare disorder caused by somatic mosaicism for the gain of function RAS mutations . Affected patients have segmental epidermal nevi, dysplastic cortical bony lesions, and fibroblast growth factor-23 (FGF23)-mediated hypophosphatemic rickets. Herein, we describe a case of an Emirati girl with CSHS, whose hypophosphatemic rickets and osteomalcic pseudofractures and dysplastic bony lesions failed to recover due to poor adherence to treatment with oral phosphate supplements and alfacalcidol (conventional treatment). Treatment with burosumab, a fully human immunoglobulin G1 monoclonal antibody against FGF23 for 12 months, led to normalization of serum inorganic phosphate and alkaline phosphatase levels, radiographic healing of rickets, partial healing of pseudofractures, improvement in 6-minute walk test, and the physical scale of the Pediatric Quality of Life Inventory. We conclude that burosumab is effective in treatment of CSHS, however results of the ongoing phase 2 trial in adults (NCT02304367) are awaited.