Impaired Physical Performance in X-linked Hypophosphatemia Is not Caused by Depleted Muscular Phosphate Stores

Context X-linked hypophosphatemia (XLH) is a rare genetic disease, characterized by renal phosphate wasting and complex musculoskeletal manifestations including decreased physical performance. Objective To characterize muscular deficits in patients with XLH and investigate phosphate stores in muscles. Methods Case-control study (Muscle fatigability in X-linked Hypophosphatemia [MuXLiH]) with a 1-time assessment at the German Aerospace Center (DLR), Cologne, from May to December 2019, including patients with XLH cared for at the Osteology Department, University of Wuerzburg. Thirteen patients with XLH and 13 age/sex/body weight-matched controls aged 18-65 years were included. The main outcome measure was P-31-magnetic resonance spectroscopy (P-31-MRS)-based assessment of phosphate metabolites in the soleus muscle at rest. Further analyses included magnetic resonance imaging-based muscle volume measurement, laboratory testing, isokinetic maximum voluntary contraction (MVC), fatigue testing, and jumping mechanography. Results By means of P-31-MRS, no significant differences were observed between XLH and controls regarding phosphate metabolites except for a slightly increased phosphocreatine to inorganic phosphate (PCr/Pi) ratio (XLH: 13.44 +/- 3.22, control: 11.01 +/- 2.62, P = .023). Quadriceps muscle volume was reduced in XLH (XLH: 812.1 +/- 309.0 mL, control: 1391.1 +/- 306.2 mv, P < .001). No significant differences were observed regarding isokinetic maximum torque (MVC) adjusted to quadriceps muscle volume. Jumping peak power and jump height were significantly reduced in XLH vs controls (both P < .001). Conclusion The content of phosphoric compounds within the musculature of patients with XLH was not observed to be different from controls. Volume-adjusted muscle strength and fatiguability were not different either. Reduced physical performance in patients with XLH may result from long-term adaptation to reduced physical activity due to skeletal impairment.