Todd and Heidi, with their daughter Ruby, living with XLH
XLH, or X-linked hypophosphatemia, is a disease that affects bones, muscles, and teeth due to the excessive loss of phosphate. Phosphate is lost through the urine, which causes low levels of phosphorus in the blood, a condition called phosphate wasting or hypophosphatemia.
Phosphate is a molecule that is made up of phosphorus and oxygen. It is required for healthy bones, muscles, and teeth. Symptoms of XLH, such as curving of the legs, or bowed legs, become noticeable at 2 years of age, a time when the legs begin to bear weight. New symptoms may also appear as the child grows. While some might think that XLH is a disease that occurs only during childhood, adults with XLH continue to experience symptoms of an ongoing disease.
XLH is an uncommon disease. Children and adults, male or female, can show varying signs and symptoms of XLH.
XLH is an inherited disease. The “X” in XLH stands for “X-linked,” because the disease is due to a defect (a mutation) in the X chromosome that can be passed onto the offspring. Males have XY chromosomes, and females have XX chromosomes.
If a mother has XLH, then her children (both boys and girls) have a 50% chance of also having XLH. This is because all children inherit one X chromosome from their mother.
If a father has XLH, all daughters will have XLH because daughters always inherit an X chromosome from their father. No sons will have XLH because sons get their X chromosome from their mother.
If a father and mother both have XLH, all daughters will have XLH, and sons have a 50% chance of having XLH.
About 20% to 30% of cases of XLH are “spontaneous”. This means that in some people with XLH, the disease is not inherited from their parents. Individuals who have a spontaneous case of XLH can still pass the disease to their children. Diagnosis of people with spontaneous cases of XLH is important.
In XLH, the body produces too much of a protein called fibroblast growth factor 23, or FGF23. This protein controls the amount of phosphate that is present in the blood. An individual with XLH has increased FGF23 activity. This makes the body behave like a leaky bucket for phosphate. People with XLH lose large amounts of phosphate through the urine, leading to hypophosphatemia.
