Diagnosis of XLH

X-linked hypophosphatemia (XLH) is a genetic disease caused by mutations in the PHEX gene and characterized by the increase of a protein called FGF23, resulting in the body losing phosphate with urine instead of retaining it. High levels of FGF23 also mean that vitamin D-dependent phosphate absorption in the intestines is blocked. This leads to decreased amounts of phosphate available in the body and results in weakened bones, among other symptoms.

The diagnosis of XLH consists of the following:

Family history and physical exam

The physician will take a complete family history of the patient to determine whether any family members have a history of XLH or symptoms that might indicate the disease. Most cases of XLH are inherited, but about 20% to 30% of cases occur because of spontaneous mutations, meaning that the parents and family members of the patient are not affected by the disease.

Symptoms that can help diagnose XLH are rickets, bowing of the legs, impaired growth, and short stature. Most people with XLH also have joint or bone pain and may walk with a distinctive, waddling gait.

X-ray imaging

X-ray imaging allows the physician to take a picture of the bones. The brightness and “texture” of the bones in the image indicate their density and strength, with weak and soft bones appearing less bright, or looking pitted and textured.

Blood tests

A small blood sample can be taken at a hospital, a clinic, or an independent laboratory and assayed for phosphate and calcium levels, as well as levels of FGF23. Test results should take a few days to a week or two to become available.

In patients with XLH, the blood tests will show very low levels of blood phosphate, and higher-than-normal levels of FGF23.

Urine analysis

The physician may ask for a urine sample to determine whether excretion levels of phosphate and calcium are within normal levels.

In XLH patients, phosphate levels in the urine will be high because the increased FGF23 in the blood prevents the kidneys from re-absorbing phosphate before urine is excreted.

Vitamin D treatment

The physician may treat the patient with vitamin D to differentiate between rickets and XLH. Vitamin D should reduce symptoms in rickets, but will not help with XLH symptoms.

Genetic testing

A genetic test can be used to confirm the diagnosis of XLH by identifying mutations in the PHEX gene.


Last updated: Dec. 8, 2019


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