Background: Hypophosphatasia (HPP) is a rare, inherited metabolic disease characterised by bone mineralisation defects and osteomalacia, and systemic manifestations, including seizures, respiratory insufficiency, muscle weakness, nephrocalcinosis, and pain. The biochemical hallmark of HPP is low serum alkaline phosphatase activity, 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 (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.
Objective: 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 collection of demographic and longitudinal clinical data.
Method: This multinational, observational, prospective, long-term registry will enroll ≧500 patients. Patients of any age with HPP will be included, except for those participating in Alexion-sponsored clinical trials. Sites will conduct the study in accordance with local regulations. Available patient data will be collected retrospectively via chart review at baseline and thereafter at intervals ≤6 months in the course of routine clinical care. Performance of new clinical procedures is not required.
Results: Data collected will include patient demographics; diagnosis methodology; HPP disease history, including dates of onset and diagnosis; family history; clinical manifestations; and genotype. 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 detailed longitudinal profile of patients with HPP, including demographics, diagnosis patterns, genotype-phenotype correlations, country-specific findings, and impact of HPP on daily activities and quality of life.
Conflict of interest: Funded by Alexion Pharmaceuticals. All authors are members of HPP Registry Scientific Advisory Board. CB, KPF, AC are employees of Alexion. PK, CRG, LS, EM, WH received honoraria from Alexion. CL, KO, AL received consultancy fees from Alexion.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology