Impaired Physical Performance in X-linked Hypophosphatemia is not caused by depleted muscular phosphate stores.

Abstract

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 XLH patients and investigate phosphate stores of the muscle. DESIGN: Case-control study (MuXLiH) with a one-time assessment at the German Aerospace Center (DLR), Cologne, from May to December 2019. SETTING: XLH patients cared for at the Osteology Department, University of Wuerzburg. PATIENTS AND PARTICIPANTS: 13 XLH patients and 13 age/sex/body weight matched controls aged 18 to 65 years. MAIN OUTCOME MEASURES: 31P magnetic resonance spectroscopy (31P-MRS) based assessment of phosphate metabolites in the soleus muscle at rest. Further analyses included MRI-based muscle volume measurement, laboratory testing, isokinetic maximum voluntary contraction (MVC), fatigue testing and jumping mechanography. RESULTS: By means of 31P-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 = 0.023). Quadriceps muscle volume was reduced in XLH (XLH: 812.1 +/- 309.0 ml, control: 1391.1 +/- 306.2 mv, p < 0.001). 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 < 0.001). CONCLUSION: The content of phosphoric compounds within the musculature of XLH patients was not observed to be different from controls. Volume-adjusted muscle strength and fatiguability were not different, either. Reduced physical performance in XLH patients may result from long-term adaptation to reduced physical activity due to skeletal impairment.