Use of burosumab in McCune Albright syndrome: case report and review of literature in mosaic disorders with FGF23 overproduction

Abstract

Increased fibroblast growth factor 23 (FGF23) related mosaic syndromes include a spectrum of disorders sharing postzygotic mutations, skin involvement and dysplastic bone lesions. This group encompasses both McCune Albright syndrome (MAS) and cutaneous-skeletal hypophosphatemia syndrome (CSHS). The altered production of FGF23 contributes to progression of the typical bone lesions of these disorders through a constant disruption of phosphate wasting and bone metabolism. In pediatric age, the current therapeutic strategies for fibrous dysplasia (FD) are able to control pain and reduce the entity of disability but not to improve disease course. FGF23 production is increased in MAS and negatively influences phosphate levels and bone metabolism. The availability of burosumab, an anti FGF23 antibody, introduced a potential new therapeutic tool for children with FD. A narrative review concerning the use of burosumab in MAS and CSHS was performed and the midterm outcome of treatment with burosumab in a 11-year-old patient with MAS and severe FD was described. The patient referred to our Center for periodic follow-up and treatment of severe FD. He was diagnosed with FD at the age of 1 year and 8 months and underwent four pathological fractures and two surgical interventions for correction of bone deformities. At the age of 5 years and 6 months, intravenous neridronate was started every 3 months with a partial improvement of bone pain and bone deformities. At the age of 8 years 9 months, subcutaneous periodic infusions of burosumab were started. Before treatment, laboratory assessment showed increased levels of FGF23 and alkaline phosphatase (ALP), and reduced phosphate with normal parathyroid hormone (PTH) levels. After 1 year of treatment with burosumab, a normalization of phosphate, ALP reduction, and normal to slightly increased PTH were observed. Nonetheless, a partial progression of FD was documented on periodic X-rays. Burosumab showed beneficial effects on bone tissue metabolisms in our patient without significant adverse effects but did not change FD course.

Keywords: FGF23; McCune Albright syndrome; burosumab; cutaneous-skeletal hypophosphatemia syndrome; fibrous dysplasia; phosphate metabolism.