Which are the symptoms of X-linked Hypophosphatemia (XLH)?

X-linked Hypophosphatemia (XLH) is a rare genetic disorder that affects the bones and teeth. It is caused by mutations in the PHEX gene, which is responsible for regulating phosphate levels in the body. This condition primarily affects males, as it is inherited in an X-linked recessive manner, but females can also be carriers of the gene mutation.

The main symptom of XLH is rickets, a condition characterized by soft, weak, and deformed bones. Rickets typically presents during childhood and can lead to various skeletal abnormalities. These may include:

• Bowed legs: The legs curve outward, causing an abnormal gait.


• Knee deformities: The knees may be abnormally close together or have an inward-facing appearance.


• Short stature: Children with XLH often have a significantly shorter height compared to their peers.


• Delayed walking: Due to weakened bones, affected children may experience delays in achieving motor milestones.


• Waddling gait: The weakened bones and muscle weakness can result in a distinctive waddling walk.


• Pain and discomfort: Individuals with XLH may experience bone pain, muscle pain, and joint pain.

Aside from skeletal abnormalities, XLH can also affect dental health. Abnormal tooth development is a common feature of this condition. The teeth may be discolored, have a pitted appearance, and be prone to cavities and enamel defects. Dental problems can lead to difficulties with chewing, speaking, and overall oral health.

Furthermore, XLH can have systemic effects on the body. Phosphate imbalance can disrupt normal cellular functions and lead to complications such as:

• Renal phosphate wasting: XLH can cause excessive loss of phosphate through the kidneys, leading to low levels of phosphate in the blood.


• Hyperparathyroidism: The parathyroid glands may become overactive in response to low phosphate levels, resulting in increased calcium levels and potential bone abnormalities.


• Hearing loss: Some individuals with XLH may experience hearing impairment, which can range from mild to severe.


• Enthesopathy: XLH can cause inflammation and pain at the sites where tendons and ligaments attach to the bones.

It is important to note that the severity and specific symptoms of XLH can vary widely among affected individuals. Some individuals may have milder forms of the condition and experience fewer complications, while others may have more severe symptoms that significantly impact their quality of life.

If you suspect that you or your child may have XLH, it is crucial to consult with a healthcare professional for a proper diagnosis and appropriate management. Treatment options for XLH may include phosphate and vitamin D supplementation, orthopedic interventions, dental care, and other supportive measures.