ESPE Abstracts

Background: X-linked hypophosphatemic rickets (XLH) is a relatively rare chronic bone metabolism disorder, caused by mutations in the X chromosome's PHEX gene. Fibroblast growth factor 23 (FGF23) levels rise, and bone metabolism is affected. The monoclonal antibody burosumab represents a novel therapeutic strategy for managing XLH, targeting the pathophysiology of the disorder. We present our experience of two XLH-diagnosed pediatric patients treated with burosumab.

Case Presentation: The first case is a male child who was referred at the age of one month. Due to known maternal illness, he had already been diagnosed with XLH. Genetic testing revealed a mutation in PHEX gene (exon 20, codon 686, c.2057 T>C hemyzygote, P.Leu686pro). For four years, the patient was treated with Pi, alphacalcidol, calcium and cholecalciferol supplements. Despite the satisfactory response of laboratory tests, the clinical improvement was suboptimal. At the age of 4^10/12, treatment with burosumab was initiated, using titrated dosage schedule. One year after treatment initiation, laboratories and height-z scores were significantly improved compared to conventional therapy. Two rickets assessment scores – namely 10-point Radiographic Score for Rickets (RSS) and RGI-C score - documented significant improvement of rachitic findings. The second case is a 3-year-old boy who was referred for genu varum and failure to thrive. Very low blood phosphorus levels and high urinary phosphorus excretion with concomitant genu varum and rachitic radiographic findings led to the diagnosis of XLH. A de novo mutation of PHEX gene (exon 16, g.22212897C>T; ENST00000379374.5: c.1646-7C>T) was found. The child was treated with conventional therapy with poor response. He initiated burosumab treatment at the age of 11^5/12. At the age of 14 years, he received additional treatment with biosynthetic growth hormone (rhGH), as he was diagnosed with growth hormone deficiency. Growth has been steadily improving, with height now being within normal ranges and laboratory results returned to normal. The patient's rickets findings have significantly improved, as evidenced by RSS and RGI-C scoring.

Conclusion: Efficacy of burosumab therapy in pediatric XLH patients is documented in many studies. Further longitudinal long-term studies and setting up of national and international databases are needed to assess real-world long-term safety and effectiveness.