XLH is a rare, hereditary*, progressive and lifelong phosphate wasting disorder, caused by mutations in the PHEX gene that leads to excess FGF23¹⁻⁴

XLH is characterised by chronic hypophosphataemia due to increased FGF23 levels2,4

Phosphate is critical to many biological functions.5 Disruption of normal phosphate homeostasis is associated with severe complications and has detrimental effects on overall health.5

In XLH, excessive levels of FGF23 decrease renal phosphate reabsorption and active vitamin D (1,25[OH]2) production, which increases urinary phosphate excretion and reduces intestinal phosphate absorption respectively; this leads to low serum phosphate levels.2,6

Excess FGF23 leads to chronic hypophosphataemia resulting in impaired bone mineralisation, severely affecting the growth and development of children with XLH.2,6

XLH is a multisystemic disease that impacts bone, muscle and dentition4

The clinical manifestations of XLH develop very early in life and usually become apparent during the first 2 years typically presenting as lower limb deformities (e.g. bowing of the legs).3,4

XLH causes rickets, progressive lower limb deformity, impaired growth, poor dental health and, in some cases, skull deformities, but the signs and symptoms can vary in severity.6

Children commonly exhibit impairments in mobility and physical function, bone and joint pain, fatigue as well as emotional and social detriments throughout childhood and adolescence.4,7

The clinical manifestations of XLH vary, and can impair physical function and quality of life6-8

XLH is a progressive, life-long disease. Unresolved childhood signs and symptoms continue to progress into adulthood.7

Potentially irreversible signs and symptoms can appear in adulthood due to ongoing active disease.7

XLH is a rare disease

A disease is defined as rare when it affects fewer than 1 in 2,000 people.9

XLH is estimated to affect approximately 1 in 20,000– 1 in 60,000 people.1,6,10 Due to its rarity, there is often a delay in diagnosis and treatment.4

XLH is inherited in an X-linked dominant pattern; however, 20–30% of cases arise from spontaneous mutations11-13

XLH is caused by mutations in the PHEX gene.4 In most cases, XLH is inherited in an X-linked dominant pattern.11

Hereditary pattern of XLH

Click the father or mother below to reveal the ratio of affected sons and daughters with an affected parent.
(dark blue indicates affected individual).

Genetic analysis can help confirm a diagnosis of XLH and identify family members who may be at risk.4

*In approximately 20–30% of cases XLH occurs spontaneously and there is no family history.11-13
1. Beck-Nielsen SS, et al. Eur J Endocrinol. 2009;160:491–497. 2. Martin A & Quarles LD. Adv Exp Med Biol. 2012;728:65–83. 3. Carpenter TO, et al. J Bone Miner Res. 2011;26:1381–1388. 4. Haffner D, et al. Nat Rev Nephrol. 2019;15:435–455. 5. Penido MGMG & Alon US. Pediatr Nephrol. 2012; 27(11): 2039–2048. 6. Beck-Nielsen SS, et al. Orphanet J Rare Dis. 2019;14(1):58. 7. Skrinar A, et al. J Endocr Soc. 2019;3(7):1321-1334. 8. Linglart A, et al. Endocr Connect. 2014;3:R13–30. 9. European Commission. Rare Diseases. Available at: https://ec.europa.eu/health/non_communicable_diseases/rare_ diseases_en. Accessed: November 2019. 10. Rafaelsen S, et al. Eur J Endocrinol. 2016;174:125–36. 11. Whyte MP, et al. J Clin Endocrinol Metab. 1996;81(11):4075–4080. 12. Rajah J, et al. Eur J Pediatr. 2011;170:1089-1096. 13. Dixon PH, et al. J Clin Endocrinol Metab. 1998;83(10):3615–3623.

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