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Children (aged 6 to 12 years; <jats:italic>n<\/jats:italic>\u2009=\u200911), adolescents (13 to 17 years; <jats:italic>n<\/jats:italic>\u2009=\u20094), and adults (18 to 65 years; <jats:italic>n<\/jats:italic>\u2009=\u20099) completed the 6MWT at screening and baseline in two clinical studies of asfotase alfa. Test\u2010retest reliability of the 6MWT, evaluated with Pearson's correlation coefficients (<jats:italic>r<\/jats:italic>) for screening versus baseline, was high for children (<jats:italic>r<\/jats:italic>\u2009=\u20090.95; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), adolescents (<jats:italic>r<\/jats:italic>\u2009=\u20090.81; <jats:italic>p<\/jats:italic>\u2009=\u20090.125), and adults (<jats:italic>r<\/jats:italic>\u2009=\u20090.94; <jats:italic>p<\/jats:italic>\u2009=\u20090.0001). The most conservative minimal clinically important differences, estimated using distribution\u2010based methods, were 31\u2009m (children and adults) and 43\u2009m (adolescents). In children, the 6MWT correlated significantly with scores on measures of skeletal disease, which included the Radiographic Global Impression of Change scale (<jats:italic>r<\/jats:italic>\u2009=\u20090.50; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and the Rickets Severity Scale (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.78; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), such that distance walked increased as the severity of skeletal disease decreased. Significant (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) correlations with the 6MWT distance walked were also observed for children with scores on parent\u2010reported measures of disability (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.67), ability to function in activities of daily living (<jats:italic>r<\/jats:italic>\u2009=\u20090.71 to 0.77), and parent\u2010reported measures of pain (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.39). In adolescents and adults, 6MWT distance walked correlated significantly (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) with measures of lower extremity function (<jats:italic>r<\/jats:italic>\u2009=\u20090.83 and 0.60, respectively), total pain severity (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.41 and \u22120.36, respectively), and total pain interference (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.41 and \u22120.49, respectively). Collectively, these data indicate that the 6MWT is a reliable, valid measure of physical functioning in patients with pediatric HPP. \u00a9 2018 The Authors. <jats:italic>JBMR Plus<\/jats:italic> Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jbm4.10131","type":"journal-article","created":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T18:07:27Z","timestamp":1544206047000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Reliability and Validity of the 6\u2010Minute Walk Test in Hypophosphatasia"],"prefix":"10.1093","volume":"3","author":[{"given":"Dawn","family":"Phillips","sequence":"first","affiliation":[{"name":"Division of Physical Therapy Department of Allied Health Sciences University of North Carolina Chapel Hill NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis C","family":"Tomazos","sequence":"additional","affiliation":[{"name":"Alexion Pharmaceuticals, Inc. 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