Burosumab in infants with X-linked hypophosphatemic rickets: a case series

BACKGROUND: X-linked hypophosphatemic rickets (XLH) is a rare inherited metabolic bone disorder caused by excess fibroblast growth factor 23 (FGF23), leading to hypophosphatemia and rickets. Burosumab, a human monoclonal antibody targeting FGF23, was approved for the treatment of XLH in April 2018. By 2022, the FDA extended its approval to include children as young as six months of age. OBJECTIVES: To describe three infants with XLH who began burosumab therapy before one year of age and were monitored for at least one year. DESIGN: Case series. METHODS: Clinical outcomes, including anthropometric measures, skeletal outcomes (Rickets Severity Score [RSS], mechanical axis deviation [MAD], and neck-shaft angle [NSA]), and laboratory parameters, were assessed in a real-world setting. RESULTS: Two patients demonstrated satisfactory linear growth, and one experienced growth faltering, possibly due to sleep-disordered breathing or phosphate imbalance. These patients received higher doses of burosumab than the current guideline recommendations for achieving treatment goals aimed at normalizing phosphate levels. The patient’s phosphate levels improved but did not normalize. Bone pain was not formally assessed, but parents reported improvements in their children’s conditions. Importantly, two patients with assessable mechanical axes demonstrated neutral mechanical axis deviations, indicating improved lower limb alignment and supporting the therapeutic efficacy of burosumab. All three patients had favorable RSS outcomes, and none developed long bone diaphyseal bowing or coxa vara following this early initiation of burosumab treatment. CONCLUSION: This case series demonstrated potential benefits of early initiation of burosumab treatment for XLH by showing improvements in growth, phosphate levels, and skeletal outcomes. Burosumab appears well tolerated in infancy, but further research is needed to refine dosing strategies and assess its long-term safety and therapeutic efficacy in young patients with XLH. Meticulous monitoring and individualized care are essential throughout treatment. This case series followed three infants with X-linked hypophosphatemic rickets (XLH) who initiated burosumab treatment at 6 months of age, filling a significant knowledge gap in early intervention. Despite requiring higher-than-recommended dosing, burosumab demonstrated favorable outcomes in terms of growth parameters and skeletal development over a minimum one-year follow-up. Two patients maintained normal growth trajectories, whereas one experienced temporary growth faltering, which resolved after adenoidectomy. Importantly, neutral mechanical axis deviation was achieved, indicating effective prevention of lower limb deformities. No significant adverse effects were observed. Despite limitations such as a small sample size and short follow-up, these findings suggest that early burosumab therapy can improve outcomes in infantile XLH patients. Further research is needed to refine dosing protocols and assess long-term safety and efficacy in this young population.