XLH (X-Linked Hypophosphatemia)

What is X-linked hypophosphatemia (XLH)?

X-linked hypophosphatemia (pronounced “high-po-faas-fuh-TEE-mee-uh”), or XLH, is a genetic disease that causes issues with your bones and teeth. It’s a form of rickets. Children with XLH often have difficulty walking and can have bowed legs. It can also cause muscle weakness, hearing loss and other issues.

What are the symptoms of XLH?

Signs and symptoms of XLH usually first appear in young kids and include:

• Difficulty walking or delay in learning how to walk.
• Bowing legs or knees that tilt toward each other (knock knees).
• Bone and muscle pain.
• Short stature.
• Low energy levels.
• Muscle weakness.
• Dental issues like very early loss of baby teeth, tooth pain, abscesses or frequent cavities.
• Physical differences in head or face shape (due to craniosynostosis).

As you get older, adults may experience additional signs and symptoms of XLH, including:

• Hearing loss.
• Headaches.
• Spinal stenosis.
• Osteomalacia.
• Balance or walking issues.
• Loss of adult teeth.
• Hardening of ligaments or tendons.
• Joint stiffness.
• Fatigue.
• Bone fractures and pseudofractures (areas that look like broken bones on X-rays but aren’t).

What causes X-linked hypophosphatemia (XLH)?

A gene change (genetic mutation) in the PHEX gene causes XLH. The PHEX gene creates FGF23 (fibroblast growth factor 23), a hormone that helps your body regulate its amount of phosphate. Phosphate is an element that keeps your bones healthy. FGF23 tells your kidneys to get rid of excess phosphate in your pee if your body has all that it needs. Your body will make less FGF23 if it needs more phosphate.

The mutation in PHEX causes your body to make too much FGF23 hormone. The excess hormones make your body get rid of more phosphate than it should. This leads to symptoms of XLH.

Is XLH inherited?

The mutation that causes XLH is inherited in an X-linked autosomal dominant pattern. This means anyone who has a gene with the mutation will have the disease. It more severely affects males.

Females have two X chromosomes and males have one X and one Y. Because you inherit one sex chromosome (an X or a Y) from each of your biological parents:

• A female who has XLH usually has a 50% chance of passing the gene on to any biological children.
• A male will pass the gene on to any female biological children but not to male children.

Sometimes, there are cases of XLH that aren’t inherited from a biological parent. In this case, the gene mutation is random and neither parent has XLH.

How is XLH diagnosed?

To diagnose XLH, a provider might order or perform these tests:

• Blood or pee (urine) tests to check phosphate and FGF23 levels.
• Genetic testing.
• Bone density tests.
• X-rays or other imaging tests.

How do you treat XLH?

There’s no cure for XLH. Treatments aim to keep your bones healthy — not to increase phosphate levels to typical levels (which might not be possible). Treatments might include:

• Phosphate supplements and calcitriol (vitamin D).
• Burosumab, a monoclonal antibody treatment that blocks FGF23.
• Physical therapy (PT).
• Occupational therapy (OT).
• Surgery to correct bone deformities.
• Growth hormones (to treat short stature).
• Hearing aids (if needed).

Additionally, you may need surgery or other procedures for broken bones or dental issues as they come up.

Can XLH be prevented?

You can’t prevent XLH. But babies diagnosed and treated with burosumab right away can grow normally and free of symptoms. If you have XLH and want to know more about the chances of passing it on to future children, talk to a genetic counselor.

What can I expect if I have XLH?

If you or your child have XLH, monitoring the condition and getting treatment early can help prevent complications. Sometimes, certain bone deformities may correct on their own or not cause any issues. Other times, they may require corrective procedures or physical therapy. Ask your provider what to expect.

What’s the life expectancy for someone with XLH?

Studies suggest that the life expectancy of someone with XLH is shorter by about eight years compared to someone without it. But experts aren’t sure what causes this difference in lifespan.

How do I take care of myself with XLH?

Some tips for taking care of yourself with XLH include:

• Get genetic testing. A positive test will allow you to start medication as soon as possible.
• Get regular dental care. This can help catch issues with your teeth and gums early.
• Attend all of your healthcare appointments and follow-ups. This includes PT and OT. Let them know about any new or worsening symptoms.
• Take any medications as prescribed. Let your provider know if you have any questions about how to take them or if you experience side effects.
• Get physical activity as recommended by your provider. They can help you select safe activities that strengthen your bones.

When should I see my healthcare provider?

If you have concerns about your child’s health, or about them meeting their developmental milestones, talk to their pediatrician. They can recommend additional testing if needed.

If you have XLH, contact your provider if you have any new or worsening symptoms.

When should I go to the ER?

Go to a dentist if you experience a dental emergency, including:

• Severe toothache.
• Badly cracked or broken tooth.
• Extruded (partially dislodged) tooth.
• Dental abscess (swelling of your face and jaw).

What questions should I ask my doctor?

It might be helpful to ask your healthcare provider:

• What are my/my child’s treatment options?
• How do I take care of my/my child’s bone health?
• When should I go to the ER?
• When should I follow up with you?

Do kids with XLH go through puberty?

Yes, kids with XLH go through puberty and have growth spurts as any other kid would.