Introduction: X-linked hypophosphatemia (XLH) is a rare, inherited disease that affects approximately 1 in 20,000 individuals. XLH is a disorder of renal phosphate wasting caused by high circulating levels of fibroblast growth factor 23 (FGF23) that impairs normal phosphate reabsorption in the kidney and production of the active form of vitamin D. Children with XLH experience abnormal bone development, rickets, osteomalacia, impaired growth, dental abscesses, craniosynostosis and bone and muscular pain. Affected adults may present with articular consequences of bone deformities, fractures, stiffness, enthesopathy, hearing loss, hyperparathyroidism, and periodontitis. As XLH is a progressive, often debilitating disease, it is important to improve understanding of both its natural history and outcomes on available therapies. Currently, there is no international registry that collects large-scale data on disease progression in XLH.
Objectives: An international, multicentre, prospective, non-interventional disease registry has recently been launched to collect natural history data and characterise the treatment, disease progression and long-term outcomes in children and adults with XLH (ClinicalTrials.gov Identifier: NCT03193476).
Methods: Design and implementation of the registry was informed by recommendations from a recent European Medicines Agency workshop (EMA/69716/2017) and approved by a steering committee of European experts. The XLH Registry is planned to run for at least 5 years aiming to recruit 1200 patients in total. Data entry is via an online data capture tool (Castor EDC, Netherlands). Patients with confirmed XLH will be included under informed consent. As a non-interventional study, all data entered will be from routine practice at the participating sites, measured at baseline and prospectively at regular intervals. No data or investigations are mandated by the protocol. The registry will collect demographic variables, age and symptoms at diagnosis, family history as well as quantitative and qualitative disease markers including: rickets, bone shape, growth, oral health, muscular function, quality of life, phosphate wasting, alkaline phosphatase and complications including nephrocalcinosis, hyperparathyroidism, hearing and neurological features.
Results: At time of submission the XLH Registry has recruited 21 patients from 11 sites across the UK, Denmark and Italy. National regulatory approval in 8 other countries is pending, with 56 sites expected to be live by December 2018.
Conclusions: The XLH Registry will generate epidemiological data that may provide improved understanding of the natural history, the disease-burden, as well as the long-term treatment outcomes of XLH. Ultimately, the XLH registry will support development of future XLH treatment guidelines and inform best practice.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology