Three Generations of X-Linked Hypophosphataemia: The Inter-generational Impact of Burosumab Across the Lifespan.

Abstract

X-linked hypophosphataemia (XLH) is a rare, lifelong heritable metabolic bone disorder characterized by fibroblast growth factor 23 (FGF23) excess, chronic hypophosphataemia, renal phosphate wasting, progressive skeletal deformities and impaired quality of life. Burosumab, targeted anti-FGF-23 therapy, is approved for use in XLH across the lifespan. Clinical trials have demonstrated benefit, although distinct outcomes in response to treatment vary depending on whether initiated during childhood, adolescence or adulthood. We uniquely describe three patients with XLH across three generations within a single family, each initiated on burosumab at different stages of life. This familial case study highlights the broad phenotypic spectrum of XLH, and differential efficacy profile of burosumab across various stages, such as pre- and post-growth plate closure or in the presence of established musculoskeletal morbidity. We also demonstrate the unique inter-generational impact of burosumab in XLH, as a targeted novel treatment available for patients with a dominantly inherited disorder across the lifespan.