Clinical manifestations in pediatric patients with XLH

XLH causes lifelong skeletal disease and can substantially decrease physical function and quality of life1,2

XLH typically presents during the first 2 years of life with progressive lower-extremity bowing, impaired growth after the onset of weight bearing, and the characteristic clinical signs of rickets. Pain, gait disturbances, and impaired gross motor function may also be observed.3,4

Children with XLH suffer from poor quality of life, impaired mobility, and bone and joint pain.2

In addition to skeletal disease and impaired growth, children with XLH may also have dental manifestations of the disease.2,5

Due to the lifelong and progressive nature of XLH,12-16 assessment is recommended
In a recent survey of 71 children with XLH, lower-extremity deformities and corrective surgeries were reported in most children younger than 2 years of age2

Growth

Children with XLH are prone to growth impairment, and linear body dimensions are significantly reduced compared to those of healthy children at all ages.17

Growth trajectory in pediatric XLH patients compared to non-XLH children aged 2-202,5
Stature, sitting height, and arm and leg length over time in children with XLH versus normal population17

While linear body dimensions are significantly reduced compared to those of normal children at all ages, there is a strong association between stature and leg length in pediatric XLH patients.17

Generally, leg length decreases progressively during childhood and adolescence, while sitting height increases significantly during late childhood.17

Dental Manifestations

XLH patients can be affected by tooth abscesses in both deciduous and permanent dentition. The disease results in a diminished barrier to the exterior of the tooth, with cracks in the thin enamel, extended pulp horns, and abnormal formation of the dentin, allowing bacteria and infections to enter the tooth pulp chamber without any visible damage to the tooth.5,18

In an international online survey of parents/caregivers of 90 children with XLH aged 0 to 18 years, it was found that 51% of children had dental abscesses and 24% had excessive caries.11

Spontaneous abscesses appear as a result of bacterial invasion into the expanded pulp chamber via the thin and fissured enamel and abnormally mineralized and malformed dentin.5,18

Children with XLH can experience diminished mobility
and functional limitations5

In children with XLH, lower-extremity muscle strength and walking ability are substantially decreased relative to non-XLH children.2

Due to the lifelong and progressive nature of XLH,12-16 assessment is recommended
Commonly reported functional limitations and pain in 71 pediatric XLH patients2
Children with XLH can have impaired quality of life (QOL)2

Skeletal manifestations of XLH impact physical and psychosocial quality of life in pediatric patients.2

Added to this, many XLH children experience regular joint pain.2

Approximately 80% of children with XLH report knee pain. Pain is also commonly experienced in the2

  • Feet
  • Hips
  • Ankles
Due to the lifelong and progressive nature of XLH,12-16 assessment is recommended
In an international survey, 71 children with XLH showed below normal results on health-related QOL assessments2
Data from the same survey showed children with XLH had heightened pain and impaired mobility relative to normal children2

1. Carpenter TO. Primary disorders of phosphate metabolism. In: De Groot LJ, Chrousos G, Dungan K, et al, eds. Endotext [internet]. South Dartmouth, MA: MDText.com. 2014;1-56. 2. Linglart A, Dvorak-Ewell M, Marshall A, et al. Impaired mobility and pain significantly impact the quality of life of children with X-linked hypophosphatemia (XLH). Poster presented at: ICCBH 2015 Salzburg, Austria. 3. Pettifor JM. What's new in hypophosphataemic rickets? Eur J Pediatr. 2008;167(5):493-499. 4. Ruppe MD. X-linked hypophosphatemia. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. Gene Reviews. https://www.ncbi.nlm.nih.gov/books/NBK83985/. Accessed October 20, 2017. 5. Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect. 2014;3(1):R13-R30. 6. Osteomalacia. Medline Plus Medical Encyclopedia. http://medlineplus.gov/ency/article/000376.htm. Updated November 6, 2017. Accessed November 16, 2017. 7. Veilleux LN, Cheung M, Ben Amor M, Rauch F. Abnormalities in muscle density and muscle function in hypophosphatemic rickets. J Clin Endocrinol Metab. 2012;97(8):E1492-E1498. 8. Rickets. MedlinePlus Medical Encyclopedia. http:// medlineplus.gov/ency/article/000344.htm. Updated November 6, 2017. Accessed November 16, 2017. 9. Chiari malformation. MedlinePlus Medical Encyclopedia. http://medlineplus.gov/chiarimalformation.htm. Updated December 23, 2016. Accessed November 16, 2017. 10. Craniosynostosis. MedlinePlus Medical Encyclopedia. http://medlineplus.gov/ency/article/001590.htm. Updated November 6, 2017. Accesssed November 16, 2017. 11. Data on file. Ultragenyx, Inc. 12. Skrinar A, Marshall A, San Martin J, Dvorak-Ewell M. X-linked hypophosphatemia (XLH) impairs skeletal health outcomes and physical function in affected adults. Poster presented at: Endocrine Society’s 97th Annual Meeting and Expo, March 5-8, 2015. San Diego, CA. 13. Martin A, Quarles LD. Evidence for FGF23 involvement in a bone-kidney axis regulating bone mineralization and systemic phosphate and vitamin D homeostasis. Adv Exp Med Biol. 2012;728:65-83. 14. Che H, Roux C, Etcheto A, et al. Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms. Eur J Endocrinol. 2016;174(3):325-333. 15. Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician's guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26(7):1381-1388. 16. Econs MJ, Samsa GP, Monger M, Drezner MK, Feussner JR. X-linked hypophosphatemic rickets: a disease often unknown to affected patients. Bone Miner. 1994;24(1):17-24. 17. Zivičnjak M, Schnabel D, Billing H, et al. Age-related stature and linear body segments in children with X-linked hypophosphatemic rickets. Pediatr Nephrol. 2011;26(2):223-231.18. Carpenter TO. New perspectives on the biology and treatment of X-linked hypophosphatemic rickets. Pediatr Clin North Am. 1997;44(2):443-466. 19. Opsahl Vital S, Gaucher C, Bardet C, et al. Tooth dentin defects reflect genetic disorders affecting bone mineralization. Bone. 2012;50(4):989-997. 20. Picture of the teeth: human anatomy. WebMD. https://www.webmd.com/oral-health/picture-of-the-teeth#1. Updated 2015. Accesssed December 9, 2017.

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