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What is XLH?

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

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Hereditary

XLH is primarily an inherited condition, which means it runs in families.

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Progressive

New symptoms of XLH may appear as patients get older and can worsen or change over time.

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Chronic

Individuals with XLH can continue to experience symptoms throughout their lives.

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XLH is hereditary, chronic, and progressive1

X-linked hypophosphatemia (XLH) is a lifelong, progressive disease characterized by hypophosphatemia due to increased fibroblast growth factor 23 (FGF23) activity.1 It is considered rare—XLH affects up to 1 in 20,000 people in the US. Although XLH is primarily an inherited disease, 20% to 30% of cases arise spontaneously.1

XLH is the most common cause of inherited phosphorus wasting and leads to poor bone mineralization, resulting in rickets and osteomalacia.1,2

You and your patients may also refer to XLH by different names:3,4

  • X-linked hypophosphatemic rickets
  • Hereditary hypophosphatemic rickets
  • X-linked dominant hypophosphatemic rickets
  • Familial hypophosphatemic rickets
  • Vitamin D-resistant rickets (VDRR)
  • X-linked vitamin D-resistant rickets
  • Hypophosphatemic rickets
  • Hypophosphatemic vitamin D-resistant rickets (HPDR)
  • X-linked rickets
  • Genetic rickets
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XLH impacts the skeletal, muscular, and dental health of children and adults throughout their lives.1

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*Actor portrayal.

What causes XLH?

Increased FGF23 activity is the underlying cause of chronic hypophosphatemia1

In normal homeostasis1

Flowchart showing how normal FGF23 activity and phosphorus levels help maintain strong and healthy bones

In normal homeostasis, FGF23 is a protein hormone produced by osteocytes in the bones that regulates serum phosphorus levels.1

In XLH1

Flowchart showing how PHEX variant causes excess FGF23, leading to chronic hypophosphatemia

In XLH, a variant in the PHEX gene causes excess FGF23, which results in phosphorus wasting leading to chronic hypophosphatemia. Due to increased FGF23 activity, patients with XLH may experience skeletal defects, muscular dysfunction, and dental abnormalities.1,5

*Actual pediatric XLH patient.
Misdiagnosis of XLH

XLH is often misdiagnosed as nutritional rickets or osteomalacia, Pyle disease (metaphyseal dysplasia), or physiologic bowing.6

Misdiagnoses may lead to an increased symptom severity.7 Learn more about and how to get an accurate diagnosis for your pediatric or adult patients.

XLH causes a substantial lifelong burden

XLH affects the entire body. Chronically low levels of phosphorus in XLH impact bone formation, dental health, muscle functioning, and energy levels. The progressive nature of the disease can leave patients susceptible to delayed growth, fractures, limited physical functioning, and pain.5,8

These issues can impact the social and emotional wellness of children and adults.5 Getting an accurate diagnosis early can help minimize the burden of XLH.

Supporting your patients

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Suspect XLH?

Connect their symptoms and diagnose with the applicable tests.

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XLH resources and community

Find resources for you and your patients to understand more about this rare condition.

Resources

References:

1. Dahir K, et al. J Endocr Soc. 2020;4(12):bvaa151. doi:10.1210/jendso/bvaa15 2. Haffner D, et al. Nat Rev Nephrol. 2019;15(7):435-455. 3. 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. 4. Fuente R, et al. Int J Mol Sci. 2022;23(2):934. 5. Hamilton AA, et al. J Endocr Soc. 2022;6(8):bvac086. 6. Carpenter TO, et al. J Bone Miner Res. 2011;26(7):1381-1388. 7. Trombetti A, et al. Nat Rev Endocrino. 2022;18(6):366-384. 8. Skrinar A, et al. J Endocr Soc. 2019;3(7):1321-1334.