Endocrine Abstracts

X-linked hypophosphatemia (XLH), representing about 80% of hypophosphatemic rickets, is an X-linked dominant disease due to inactivating mutations in the PHEX gene (located at Xp22.1) resulting in an excessive secretion of the phosphaturic hormone fibroblast growth factor 23 (FGF23). The effects are renal phosphate wasting and reduced active vitamin D synthesis leading to rickets, osteomalacia, bone deformities, odontomalacia, frequent dental abscesses and disproportionate short stature. Conventional therapy, based on phosphate and/or active vitamin D supplementation, heals the active radiological lesions of rickets and improves statural growth but doesn’t prevent the clinical manifestations of the disease and is associated to potential side effects such as nephrolithiasis, nephrocalcinosis and hyperparathyroidism. Since 2018 burosumab, a fully humanized monoclonal antibody against FGF-23, has been authorized for patients affected by XLH on the basis of promising results from different clinical trials in adults and children. However, all studies include severely affected patients and very few data on the effects of burosumab in everyday setting are available. We present the response to one-year treatment with burosumab injected subcutaneously at 1 mg/kg every four weeks in two patients belonging to the same family namely patient 1 (mother, aged 54 years) and patient 2 (son, aged 19 years), with a genetically confirmed diagnosis of XLH, due to a splice site mutation in the PHEX gene. Of note, patient 2 was on conventional therapy with oral phosphate and calcitriol which was suspended one week before the beginning of burosumab. Both patients had bone deformities, such as varus knee and scoliosis. Patient 1 had undergone multiple orthopedic interventions during childhood and suffered from limb stiffness and severe arthralgias with functional limitations. Patient 2 was in general good conditions but developed recurrent dental abscesses. In both patients burosumab led to rapid normalization of phosphate levels and increase of tubular reabsorption of phosphate (TRP) and TmP/GFR. Serum PTH and bone alkaline phosphatase (BAP) levels were not significantly modified during treatment. Burosumab was well-tolerated, with overall adverse events of mild severity, such as transient nausea, diarrhea, skin lesions, muscle cramps and arthralgia. In patient 2, only one episode of dental abscess occurred during burosumab treatment. BPI and WOMAC questionnaires, assessing the severity of pain, stiffness and physical functioning respectively, were administrated at each visits showing a great improvement of scores. In conclusion, in our patients burosumab has been proven to be effective and safe allowing a significant improvement in quality of life.