X-linked Hypophosphatemia (XLH), the most common heritable form of rickets, is a disorder of renal phosphate wasting caused by high circulating levels of fibroblast growth factor 23 (FGF23) that impairs normal phosphate reabsorption in the kidney and production of the active form of vitamin D. Affected children present with hypophosphatemia resulting in rickets, bowing of the legs and short stature. Limited information is available about the disease burden in children with XLH.
Objectives: The objective was to characterize the clinical condition of children with XLH and assess the impact on function and quality of life.
Methods: An IRB-approved, web-based questionnaire was completed by parents on behalf of children with XLH. Pain and disability were assessed by parent report using the POSNA PODCI (Pediatric Orthopedic Society of North America Patient Outcomes Data Collection Instrument) and SF-10 Health Survey for Children. English and French versions were available.
Results: 71 pediatric surveys were completed for children from 117 years of age with a median age of 8 years (9 in the 04, 48 in the 512, 14 in the 1218 age groups respectively). Reported skeletal abnormalities included bowing of the tibia/fibula (52/71 (73%)), bowing of the femur (45/71 (63%)), gait disturbance (61/71 (86%)), joint pain (46/71 (65%)), bone pain (42/71 (59%)), joint stiffness (30/71 (42%)) and short stature (57/71(80%)). Over 30% of responders had undergone at least one surgery to correct a skeletal defect. Mean POSNA PODCI domain scores for XLH children with bone or joint pain were as follows: transfer and basic mobility 40.8 (18.6), Sports and physical functioning 29.4 (19.6), pain/comfort 34.3 (16.1), happiness 35.0 (17.5) and global functioning 35.0 (17.2). The mean SF-10 physical health summary (PHS) score for children with bone or joint pain was 33.5 (16.4). Scores were similar in the 512 and 1218 age groups. For all PODCI and SF-10 scales, the mean score in a general population of healthy children is 50 (S.D.=10) with higher scores indicating better health.
Conclusion: Children with XLH experience significant skeletal deformity with associated bone pain, joint pain, and joint stiffness that restrict range of motion, impair gait and diminish physical health status relative to peers. Limitations of this study include the small sample size, particularly in early childhood and adolescence, and the responder selection bias associated with the use of an online survey.
Disclosure: Authors associated with Ultragenyx Pharmaceutical Inc. are employees of Ultragenyx Pharmaceutical Inc. which is the company that sponsored the study
27 - 30 Jun 2015