Burden of Disease in Hypophosphatasia (HPP)

Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by inactivating mutations in the Alkaline Phosphatase (ALPL) gene, coding for the Tissue-nonspecific alkaline phosphatase (TNAP). Penetrance and disease severity is very heterogenous, ranging from stillbirth to adult-onset manifestations. Especially the latter are again characterized by an extremely broad spectrum of symptoms. This scope of variability makes it difficult to attribute individual patients' symptoms to the disease and distinguish them from HPP independent health issues. Especially in adult HPP patients, musculoskeletal problems, including (fragility-) fractures / bone bruise, joint pain, reduced mobility, muscular weakness and pain and reduced muscular endurance appear to reflect the prevailing burden of disease, especially with respect these patients dis-abilities of daily life. To expand current knowledge of the natural history of the disease as well as on disease specific musculoskeletal deficits in HPP, all adult patients with established Diagnosis of HPP known at the Orthopedic Institute, University of Würzburg, will be offered to participate in a single, multimodal assessment of their disease history, current symptoms and disabilities, lab evaluations and clinical and technical analysis of their musculoskeletal status and capabilities. Patients will be invited to a day long visit to the clinic in order to perform the following assessments: A) Epidemiologic / anamnestic information B) Physical examination C) Structured questionnaires D) Laboratory examinations E) Clinical functional testing F) Technical Examinations