ESPE Abstracts

Cutaneous skeletal hypophosphatemia syndrome (CSHS) is a rare mosaic disorder caused by somatic gain-of-function RAS mutations. It is characterized by segmental epidermal nevi and fibroblast growth factor-23 (FGF23) mediated hypophosphatemic rickets. These patients also have dysplastic cortical skeletal lesions. We describe an Emirati child with CSHS whose hypophosphatemic rickets and dysplastic skeletal lesions failed to heal due to poor adherence to conventional oral phosphate supplements and alfacalcidol treatment. The diagnosis of CSHN with FGF23-mediated hypophosphataemic rickets was made in our patient due to increased urinary phosphate excretion and hypophosphatemia in the face of normal serum PTH levels and inappropriately elevated plasma FGF23 levels. The whole-exome sequence on cells from nevoid skin biopsy revealed a somatic missense variant c.182A>G p.(Gin61Arg) (chr11:533874;hg19) in the HRAS gene (OMIM *190020; chromosome 11p15.5). Burosumab, a fully human immunoglobulin G1 monoclonal antibody to FGF23, has been approved for treating children with X‐linked hypophosphatemia (XLH), a multisystem disorder caused by increased expression of FGF23. Treatment of our patient with Burosumab for 36 months resulted in normalization of her serum inorganic phosphate and alkaline phosphatase levels, healing of rickets, improvement in her linear growth, symptoms of myopathy, and quality of life. In summary, we report the successful long-term treatment of hypophosphatemic rickets in CSHS with Burosumab over 36 months. Burosumab showed promising efficacy and safety profile in our patient, without any side effects. This success may help in the approval of this targeted therapy for CSHS.