Disease Directory X-Linked Hypophosphatemia
Connective Tissue

X-Linked Hypophosphatemia

Also known as: XLH, X-linked hypophosphatemic rickets, PHEX mutation, vitamin D-resistant rickets

Prevalence

1 in 20,000

Onset

Early childhood (typically age 1–2 when walking begins)

Type

Genetic — X-linked dominant

Gene

PHEX

About X-Linked Hypophosphatemia

X-linked hypophosphatemia is the most common hereditary form of rickets, caused by loss-of-function variants in PHEX, a phosphate-regulating endopeptidase that normally suppresses FGF23 production; PHEX deficiency leads to inappropriately elevated circulating FGF23, renal phosphate wasting, and impaired vitamin D activation. The resulting hypophosphataemia causes defective skeletal mineralisation, bowed legs, growth retardation, dental abscesses from abnormal dentine, and musculoskeletal pain throughout life. Burosumab, an anti-FGF23 monoclonal antibody, represents targeted therapy and has transformed the treatment landscape.

Common Clinical Features

Bowing of the lower limbs appearing when weight-bearing begins Short stature and growth retardation Rachitic changes on skeletal radiography Dental abscesses without obvious dental caries due to abnormal dentine Bone pain and muscle weakness Craniosynostosis in childhood Enthesopathy (calcification of tendons and ligaments) in adults

Clinical Trial Eligibility Tips

What to know before applying to X-Linked Hypophosphatemia trials.

Serum phosphorus, TRP (tubular reabsorption of phosphate), and FGF23 levels are key biomarkers at screening — ensure these are drawn fasting and that current conventional therapy (phosphate and calcitriol) is documented.

Prior or current burosumab treatment is a frequent exclusion criterion in investigational trials; confirm last dose date and current treatment regimen with the trial coordinator.

Wrist and knee radiographs graded for rachitic severity (Thacher score or equivalent) are standard baseline requirements in paediatric trials.

Patient Resources

Patient Organization

XLH Network

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Natural History Registry

XLH Registry

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Orphanet

European reference resource for rare diseases (ORPHA:89936)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

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Find recruiting X-Linked Hypophosphatemia trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for X-Linked Hypophosphatemia. Updated daily.

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