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  • X-linked hypophosphatemia (XLH) is a rare genetic disease that causes your body to release phosphorus through your urine.
  • The excessive wasting of phosphorus leads to low levels of phosphorus in the blood, known as hypophosphatemia, which can cause damage to teeth and bones.
  • Identifying and treating XLH can help to address symptoms and improve quality of life.

While many cases of X-linked hypophosphatemia are inherited, some people experience this condition with no family history. Recognizing the symptoms and finding the right treatment can help to minimize bone damage.

Read on to learn about X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is a rare, inherited disease. If you have it, your kidneys don’t process phosphate well in your blood and expel it out with urine.

Phosphorus is important for bone and teeth development and health. It also contributes to cell structures and energy production.

To compensate, your bones release phosphate into the blood. Your bones and teeth need phosphate for both building and repairs. The lack of the mineral causes the bones to soften, a condition known as rickets.

XLH is a rare disease. It affects 1 out of every 20,000 people.

It’s also inherited. This means a parent with the condition may pass it on to their children.

XLH is known by several names. According to the National Organization for Rare Disorders, XLH is also known as:

  • hereditary type I hypophosphatemia (HPDR I)
  • familial hypophosphatemia
  • X-linked hypophosphatemia
  • hypophosphatemic D-resistant rickets I
  • phosphate diabetes
  • hereditary type II hypophosphatemia (HPDR II)
  • hypophosphatemic D-resistant rickets II
  • X-linked vitamin D-resistant rickets

XLH is an inherited disease. In other words, if your biological parent has the condition, you may inherit it.

However, you may also develop XLH with no family history. About 20 percent of people living with XLH have no family history of the condition.

Inheritance of the condition can come from either parent on the X chromosome, which is why it’s referred to as “X-linked”.

According to the Genetic and Rare Diseases Information Center, your chances of passing to your children varies based on your sex:

  • females have a 50 percent chance to pass on to each child
  • males have a 100 percent chance to pass on to female children and a 0 percent chance of passing on to male children

Males have a higher risk of developing the condition due to only having one X chromosome.

Doctors typically diagnose the condition during childhood.

XLH occurs due to a mutation in the PHEX gene located on the X chromosome. The Endocrine Society states that the PHEX gene is responsible for regulating the amount of phosphate in your body.

A change to this gene causes your kidneys to filter too much phosphate from your body through the urine, which is known as phosphate wasting.

The XLH Network identifies different bone and teeth development as a primary symptom of XLH. They also indicate that many people develop rickets (softened bones) as a result of the condition.

Some other common symptoms can include:

  • pain in bones
  • muscle weakness or pain
  • atypical or waddling gait
  • shorter stature
  • slowed growth rate
  • spontaneous tooth abscesses

The Genetic and Rare Diseases Information Center adds that if you develop rickets with XLH, therapies that could work in other cases (such as taking vitamin D alone) won’t have a major impact. Additional XLH symptoms can include:

  • tendon and ligament calcification, leading to joint pain
  • uncommon tooth development or pain
  • impaired mobility

Results from a 2019 survey in people with XLH and those caring for children also indicated a psychosocial impact, especially when children aren’t able to participate in physical activities due to their symptoms.

The International XLH Alliance notes a difference in symptoms between children and adults:

  • Children: disproportionate or slowed growth, rickets, craniosynostosis, and delayed motor development and walking gait
  • Adults: osteoarthritis, bone fractures, calcifications on various joints, disability, and hearing loss

There are several factors your or your child’s doctor looks for when making a diagnosis. The doctor will likely assess you or your child with:

  • blood samples and tests
  • imaging, such as an X-ray
  • discussion of family history
  • a physical exam

They are typically looking for factors such as:

  • bowing of the legs or other different developments in the skeleton
  • slow growth rate
  • reduced phosphate levels, even after vitamin D treatment
  • kidneys wasting phosphate
  • blood with low levels of phosphate and high levels of fibroblast growth factor-23 (FGF23), which helps to regulate phosphate levels in the blood

Early diagnosis and treatment can help improve your outcome. Treatment can help curb symptoms and may encourage positive growth and development.

The main goal of treatment is to get more phosphate into the blood. Traditionally, this has been accomplished through daily phosphate supplements. Your doctor may also prescribe or recommend vitamin D supplements.

A newer medication, burosumab (Crysvita), works by targeting the excess hormone that affects phosphate levels, FGF23. This medication is an injection administered by a doctor every few weeks.

In some cases, your doctor may recommend surgery to help correct bone deformities.

Maintain your oral health by brushing your teeth and keeping them as clean as possible. Regular dentist visits can help with this as well.

Conditions related to XLH have similar symptoms but are different conditions with differing treatments. According to the Genetic and Rare Diseases Information Center, some related conditions include:

  • renal Fanconi syndrome
  • autosomal dominant hypophosphatemic rickets
  • tumor-induced osteomalacia
  • autosomal recessive hypophosphatemic rickets
  • hereditary hypophosphatemic rickets with hypercalciuria
  • vitamin D deficiency
  • fibrous dysplasia of bones

You should talk with your or your child’s doctor if you suspect XLH. It’s possible they may discover the condition during a routine visit or when reviewing your family history.

Your doctor may be able to recommend a specialist in your area. You should look for a doctor familiar with the condition and the latest treatment options available.

With regular phosphate treatment, you’ll likely experience a decrease in symptoms. However, if you are an adult, you may not notice any improved changes in height or growth.

Regular and consistent treatment can help to decrease the severity of symptoms and prevent them from getting worse.

If you or your child has XLH, phosphate supplements or medication will be necessary to treat the condition. Talk with your or your child’s doctor about what treatments may be best.

Regular and consistent treatment can help prevent new issues, stop symptoms from getting worse, and improve quality of life.