DISEASE OVERVIEW

 

What is XLH?

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

Rickets and osteomalacia: X-linked hypophosphatemia signs

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

X-linked hypophosphatemia impacts skeletal, muscular, and dental health in children and adults

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

X-linked hypophosphatemia inheritance and spontaneous cases

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 hypophosphatemic rickets2,5,6

  • Hereditary hypophosphatemic rickets7

  • Familial hypophosphatemic rickets2,5

  • Vitamin D–resistant rickets (VDRR)2

  • Vitamin D–resistant osteomalacia8

  • X-linked vitamin D–resistant rickets2

  • Hypophosphatemic rickets2

  • Hypophosphatemic vitamin D–resistant rickets (HPDR)2

  • X-linked rickets (XLR)2

  • Genetic rickets5

  • Familial hypophosphatemia5

UNDERLYING CAUSE OF XLH

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

Increased FGF23 activity is the underlying cause of chronic hypophosphatemia

PATIENT IMPACT

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

pediatric patient

Effects of XLH in children include stunted growth, pain, leg abnormalities, and decreased physical health

adult patient

Effects 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 hypophosphatemia. J Bone Miner Res. 2011;26(7):1381-1388. 2. Ruppe MD. X-linked hypophosphatemia. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews®. University of Washington, Seattle; 1993-2022. Published February 9, 2012. Updated April 13, 2017. https://www.ncbi.nlm.nih.gov/books/NBK83985/ 3. Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphatemic 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 hypophosphatemic rickets. Hum Genet. 2009;125(4):401-411. 5. Fuente R, García-Bengoa M, Fernández-Iglesias Á, Gil-Peña H, Santos F, López JM. Cellular and molecular alterations underlying abnormal bone growth in X-linked hypophosphatemia. Int J Mol Sci. 2022;23(2):934. 6. X-linked hypophosphatemia. Genetic and Rare Diseases Information Center (GARD). Updated February 26, 2018. Accessed March 14, 2022. https://rarediseases.info.nih.gov/diseases/12943/x-linked-hypophosphatemia 7. Hereditary hypophosphatemic rickets. Genetics Home Reference.Updated August 18, 2020. Accessed March 14, 2022. https://ghr.nlm.nih.gov/condition/hereditary-hypophosphatemic-rickets 8. Wang M, Cao X, Cao B. Hypophosphatemic 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.