Hereditary, progressive, and lifelong disease

 

X-linked hypophosphataemia (XLH) is characterized by chronic hypophosphataemia due to increased fibroblast growth factor 23 (FGF23) activity.1,2

XLH leads to softening of bones called rickets and osteomalacia

XLH leads to poor bone mineralization resulting in rickets and osteomalacia, the sources of progressive and compounding symptoms leading to skeletal defects, muscular dysfunction, and dental abnormalities.1-3

XLH affects children and adults

XLH impacts the skeletal, muscular, and dental health of children and adults throughout their lives.1-3

XLH is inherited

XLH is inherited within families but about 20% to 30% of cases may arise spontaneously.4 Ask about a patient’s family history for an accurate diagnosis.

You and your patients may also know XLH by these names:

  • X-linked hypophosphataemic rickets2,5,6
  • Hereditary hypophosphataemic rickets7
  • Familial hypophosphataemic rickets2,5
  • Vitamin D–resistant rickets (VDRR)2,5
  • Vitamin D–resistant osteomalacia8
  • X-linked vitamin D–resistant rickets2
  • Hypophosphataemic rickets2
  • Hypophosphataemic vitamin D–resistant rickets (HPDR)2
  • X-linked rickets (XLR)2
  • Genetic rickets5
  • Familial hypophosphataemia5

In normal homeostasis, FGF23 is a protein hormone mainly produced by osteocytes in the bones to regulate serum phosphate levels.9

In XLH, there is an increased FGF23 produced in the bones

In XLH, an X-linked dominant genetic variant of the PHEX gene causes increased FGF23 activity, which leads to chronic hypophosphataemia1,2,9

In XLH, phosphorus is wasted in the kidneys

Increased FGF23 activity decreases renal phosphate reabsorption, which increases urinary phosphate excretion and decreases calcitriol production1,9

In XLH, the small intestine does not produce enough vitamin D

Decreased levels of calcitriol reduce intestinal phosphate absorption1,9

Increased FGF23 activity leads to chronic hypophosphataemia manifesting as rickets and osteomalacia in children and osteomalacia in adults, the sources of compounding symptoms in XLH.1-3

pediatric patient

Consequence of XLH in children include delayed growth, pain, leg deformities, and decreased physical function

adult patient

Consequence of XLH in adults include fractures, stiffness, pain, and decreased physical function

References:

1. Carpenter TO, Imel EA, Holm IA, Jan de Beur SM, Insogna KL. A clinician’s guide to X-linked hypophosphataemia. J Bone Miner Res. 2011;26(7):1381-1388. 2. Ruppe MD. X-Linked Hypophosphataemia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017. 3. Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphataemic rickets from infancy to adulthood. Endocr Connect. 2014;3(1):R13-30. 4. Gaucher C, Walrant-Debray O, Nguyen TM, Esterle L, Garabedian M, Jehan F. PHEX analysis in 118 pedigrees reveals new genetic clues in hypophosphataemic rickets. Hum Genet. 2009;125(4):401-411. 5. What is XLH? XLH Network Website. https://xlhnetwork.org/what-is-xlh/. Updated August 13, 2017. Accessed January 3, 2019. 6. X-linked hypophosphataemia. Genetic and Rare Diseases Information Center (GARD) Website. https://rarediseases.info.nih.gov/diseases/12943/x-linked-hypophosphataemia. Updated 2018. Accessed January 3, 2019. 7. Hereditary hypophosphataemic rickets. Genetics Home Reference Website. https://ghr.nlm.nih.gov/condition/hereditary-hypophosphataemic-rickets. Updated January 2, 2019. Accessed January 3, 2019. 8. Wang M, Cao X, Cao B. Hypophosphataemic vitamin D-resistant osteomalacia: a case report. Exp Ther Med. 2013;6(3):791-795. 9. 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.