Objective: Hypophosphatasia (HPP) is a rare, inherited metabolic disease characterized by bone mineralization defects and osteomalacia, as well as systemic manifestations, including seizures, respiratory insufficiency, muscle weakness, nephrocalcinosis, and pain. The biochemical hallmark of HPP is low serum alkaline phosphatase, resulting from loss-of-function mutations in the gene encoding tissue non-specific alkaline phosphatase. HPP presents a broad spectrum of disease severity classically defined by age at onset of symptoms (perinatal/infantile, juvenile, adult, odontohypophosphatasia (isolated dental symptoms only), and benign prenatal), with recognized overlap between, and range of severity within, these forms. The rarity of HPP combined with its variable expressivity presents considerable challenges in the diagnosis and understanding of the disease. Here we describe the design of an HPP Registry, which will enable better characterization and understanding of the epidemiology and clinical course of HPP through prospective collection of demographic and longitudinal clinical data.
Methods: This multinational, observational, prospective, long-term registry will enroll at least 500 patients, beginning with a 6-site pilot study to assess effectiveness of the protocol. Patients of any age with HPP will be included, except for those participating in an Alexion-sponsored clinical trial. Sites will conduct the study in accordance with local regulations. Patient data will be collected retrospectively at baseline and thereafter at intervals of at least every 6 months in the course of routine clinical care. The protocol details data to be collected, recognizing that not all requested data will be available at all sites; performance of new clinical procedures is not required. Chart review and patient-reported data will be assessed. Retrospective data collection will focus on patient demographics and HPP disease history, including dates of onset and diagnosis; family history; clinical manifestations; biochemical testing; and genotype, if available. Data from medical and laboratory assessments specific to HPP will be recorded. Standardized questionnaire instruments will be used to quantify patient-reported burden of disease, functional status/disability and quality of life.
Conclusion: The HPP registry will provide a comprehensive real-life longitudinal profile of patients with HPP, including demographics, diagnosis patterns, genotype-phenotype correlations, country-specific findings, and impact of HPP on activities of daily living and quality of life.
Disclosure: Funded by Alexion Pharmaceuticals. All authors are members of the HPP Registry Scientific Advisory Board.
Camille Bedrosian, Kenji P. Fujita, and Alex Cole are the employees of Alexion Pharmaceuticals Inc.
Priya Kishnani, Cheryl Rockman-Greenberg, Lothar Seefried, Etienne Mornet, Keiichi Ozono, and Wolfgang Högler have received honoraria from Alexion Pharmaceuticals Inc.
Craig Langman and Agnes Linglart have received consultancy fees from Alexion Pharmaceuticals Inc.
27 - 30 Jun 2015