X-Linked Hypophosphatemia (XLH) is a rare genetic disorder that affects about one in 20,000 people. The key characteristic of XLH is a low level of phosphorus in the blood, called Hypophosphatemia. When a person is affected by XLH, their kidneys do not properly handle Vitamin D and phosphorus. This causes a variety of symptoms and disorders that affect their bones and teeth.
X-linked hypophosphatemia (XLH) is a rare genetic disorder characterized by low levels of phosphate in the blood. Phosphate levels are low because phosphate is abnormally processed in the kidneys, which causes a loss of phosphate in the urine (phosphate wasting) and leads to soft, weak bones (rickets) leading to many symptoms, further outlined below.
The symptoms of XLH can vary in severity. Some people with XLH have no apparent bone-related symptoms and only hypophosphatemia, while others have severe symptoms. In many cases, symptoms become apparent within the first 18 months of life, when a child begins to bear weight on the legs. Early signs and symptoms may include abnormal bone development (leading to bowing or twisting of the lower legs) and short stature or a slowing growth rate. Other symptoms that may be present early or may develop include:
In some cases, symptoms of XLH do not begin until adulthood. Symptoms that may develop in adults with XLH include joint pain and impaired mobility from enthesopathy (calcification of the tendons, ligaments, and joint capsules), tooth abscesses, and hearing loss.
For more details on the symptoms of XLH, please visit here.
People with XLH have a mutation in the PHEX gene, which causes the body to produce too much of a hormone called fibroblast growth factor 23 (FGF23). FGF23 controls the amount of phosphate present in the blood.
Too much FGF23 causes phosphate wasting, the loss of phosphate through urine. Phosphate wasting leads to low levels of phosphorus in the blood, a condition called hypophosphatemia. This leads to weak and soft bones, the underlying cause of the symptoms of XLH
XLH is different from other types of rickets because it cannot be treated by increasing vitamin D alone.
Currently there are two main treatments for XLH:
The first is with Phosphate supplements combined with a high dose of Calcitriol. Calcitriol increases calcium levels by increasing the amount of calcium absorbed in the intestines and the amount of calcium kept in the kidneys.
The second is Burosumab (brand name: Crysvita), a new Health Canada and FDA approved prescription medicine that targets the root cause of the disease by blocking the FGF23 hormone’s activity helping to restore the phosphorus absorption in the kidneys.
Other treatments for XLH, depending on symptoms and severity, may include: