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X-linked hypophosphatemia (XLH) arises due to inactivating mutations of the PHEX gene resulting in elevated circulating levels of the hormone FGF23, producing phosphaturia and impaired intestinal phosphate absorption. XLH is a lifelong metabolic disease with musculoskeletal comorbidities that dominate the adult clinical picture, and are resistant to standard therapies. We have previously reported the physical and functional impact of the adult disorder (J Clin Endocrinol Metab. 2020 Apr 1;105(4)). Bilateral and diffuse enthesophytes, degenerative arthritis and osteophytes were reported at the spine and synovial joints across subjects. Passive range of motion (ROM) was decreased at the spine, hips, knees, and ankles compared to controls. Gait analysis, relative to controls, revealed increased step width, markedly increased lateral trunk sway, and physical restriction at the hip, knees and ankle joints that translated into limitations through the gait cycle. These studies have been translated into an evidence-based physical therapy (PT) intervention study to address these major physical and functional comorbidities. Participants were enrolled in a remote 12-week PT program consisting of balance exercises and basic stretches with/without resistance. Subjects were evaluated at baseline and at every 4-weeks to assess ROM, gait, and functional ability. Several validated tools were employed to assess overall function: Berg Balance Scale, the Timed Up and Go (TUG) Test, and the Five Times Sit to Stand Test (5XSST). Subjective questionnaires, including the Lower Extremity Functional Scale (LEFS) and Activities-Specific Balance Confidence (ABC) Scale, were administered along with a weekly survey. At the conclusion of the study, minimal to modest improvements were seen in active ROM for the upper and lower extremity which reflect the significant bony restriction caused by XLH. However, improvements were seen in functional measures including the Berg Balance Scale, TUG, 5XSST, LEFS, and ABC. Weekly surveys indicated that participants improved their ability to balance, perform activities of daily living (ADLs), walk, and bend down to reach the ground. Results from this study will be applied to the creation of an evidence-based PT program to maintain functional capacity and improved ability to perform ADLs across the lifespan.

Creation of an Evidence-Based Physical Therapy Program for Adults with XLH: Translational Application of an Interprofessional Clinical Study