Burosumab Treatment for Autosomal Recessive Hypophosphatemic Rickets Type 1 (ARHR1).

CONTEXT: Autosomal recessive hypophosphatemic rickets (ARHR) are rare, heritable renal phosphate-wasting disorders that arise from overexpression of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) leading to impaired bone mineralization (rickets and osteomalacia). Inactivating mutations of Dentin matrix protein 1 (DMP1) give rise to ARHR type 1 (ARHR1). Short stature, prominent bowing of the legs, fractures/pseudofractures, and severe enthesopathy are prominent in this patient population. Traditionally, treatment consists of oral phosphate replacement and the addition of calcitriol but this approach is limited by modest efficacy and potential renal and gastrointestinal side effects. OBJECTIVE: The advent of burosumab (Crysvita), a fully humanized monoclonal antibody to FGF23 for the treatment of X-linked hypophosphatemia and tumor-induced osteomalacia, offers a unique opportunity to evaluate its safety and efficacy in patients with ARHR1. RESULTS: Monthly administration of burosumab to 2 brothers afflicted with the disorder resulted in normalization of serum phosphate, healing of pseudofracture, diminished fatigue, less bone pain, and reduced incapacity arising from the extensive enthesopathy and soft tissue fibrosis/calcification that characterizes this disorder. No adverse effects were reported following burosumab administration. CONCLUSION: The present report highlights the beneficial biochemical and clinical outcomes associated with the use of burosumab in patients with ARHR1.