Introduction: XLH is caused by mutations in PHEX leading to increased FGF23 levels, phosphate wasting, and impaired endogenous calcitriol synthesis. Affected patients present with rickets and diminished growth velocity during childhood, and osteomalacia and short stature in adulthood. Adult height is linked with health within and across generations suggesting that adult height may be a potential tool for monitoring health conditions, e.g., XLH.
Methods: Observational study based on medical records of final heights in men and women with XLH grouped according to their birth year, 1950-1975, 1976-2000, and 2001-2006. XLH was assessed by biochemistry and X-linked inheritance and/or a mutation in PHEX. Final height was defined by height reached after 18 years or 16 years and growth velocity <2 cm /year. Pearson’s correlation test (R software) was used to evaluate the evolution of final heights. Comparison with healthy peers was made using WHO references.
Results: Final heights from 398 XLH patients were recorded (278 females). Patients born between 1950 and 1975 (n=127, mean age 26.1 yrs at study) have a mean final height of -2.31 (SD 1.11); patients born between 1976 and 2000 (n=193, mean age 20.6 yrs) have a mean final height of -1.63 (SD 1.13) and patients born between 2001 and 2006 (n=78, mean age 17.3 yrs) have a mean final height of -1.34 (SD 0.87). There is a significant increase in mean final heights between birth year groups for men and women (P = 3.8 x 10-14). In addition, the mean final height in men [-2.08 (SD 1.18), i.e., 160.5 cm] is significantly smaller than that of women with XLH [-1.70 (SD 1.12), i.e., 151.7 cm], (P=0.002).
Conclusion: Our study shows that final height can be used to monitor global health in XLH. Similar to other studies, our results suggest that, for XLH, males may display more severe disease than females. More importantly, we show that the final height in patients with XLH has significantly improved over the last decades in France which very likely reflects better disease management. Final height increased the most for patients born before 1975 and between 1975 and 2006. In fact, vitamin D analogs were added to phosphate supplements for the treatment of XLH in the late 1970s; the organization of care including multidisciplinary clinics, and reference centers for rare diseases were developed in France in the early 2000s. Another 10-15 years will be necessary to evaluate the benefit of burosumab on final heights.
15 Sep 2022 - 17 Sep 2022