X-linked hypophosphatemic rickets (XLH) is the most common form of hereditary rickets. It is caused by inactivating mutations in the PHEX gene (phosphate-regulating-endopeptidase-analog, X-linked), leading to increased fibroblastic growth (FGF-23) levels, responsible for the renal phosphate wasting. This results in hyperphosphaturia and hypophosphatemia, and altered bone mineralization, in the absence of vitamin D deficiency. Classical treatment consists on oral supplementation of phosphate and bioactive forms of vitamin D. Recently, the European Medicines Agency approved the use of Burosumab, an anti-FGF-23 monoclonal antibody, in patients older than one year with radiographic signs of bone disease. We present the case of a 6-year-old male patient, attended initially at the age of 21 months, for severe genu varum and radiographic signs of rickets. The tests performed revealed normocalcemia and normomagnesemia, with hypophosphatemia (2.2 mg/dl, NV 3.87.5), hyperphosphatasemia (539 U/l, NV 40462) and decreased tubular phosphate reabsorption (TPR) in 24-hour urine (70%; NV >85%), without hypercalciuria (3 mg/kg/day, NV <4 mg/kg/day), increased levels of intact PTH (77pg/ml, NV 1565) and 1,25(OH)2-Vitamin D (106 pg/ml; VN 1656) with normal 25 (OH)-vitamin D (24.9) ng/dl; VN 21100), and normal lumbar bone densitometry (Z score −0.1 SDS). Plasma FGF-23 levels were markedly increased (>427 RU/ml; NV <145), and genetic testing confirmed the clinical diagnosis, showing a mutation in exon 6 of PHEX gene in hemicigosis. He received conventional therapy for 4 years, with adequate adherence, with no clinical or biochemical response, requiring hemiepiphysiodesis of the distal femur and bilateral proximal tibia due to significant deformity, which rendered no positive results and were eventually removed. He started burosumab therapy at 0.8 mg/kg every 15 days due to an early access program. No local or systemic adverse events appeared. He has now completed 22 weeks of therapy and there has been an improvement in phosphorus levels (3.5 mg/dl), phosphatases (326 U/L) and TPR (98%), correction of hyperparathyroidism, as well as an improvement of the lower limbs deformities and bone density gain (Z-score 1.8 SDS). In addition, the family refers improvement in quality of life, with greater mobility and less effort to perform physical exercise. In our case, burosumab therapy has been effective clinically and biochemically, with no adverse events up to date. However, the follow-up is still too short to evaluate long term benefits and clinical outcome.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology