X-linked hypophosphatemia (XLH) is a genetic disorder that causes low levels of phosphorus in the blood and affects bones, muscles, and teeth. XLH causes an excess amount of phosphate to be eliminated by the kidneys in the urine (otherwise known as phosphate wasting or hypophosphatemia). Phosphate is a mineral that is important for the normal formation of bones and teeth.
XLH is typically an inherited disease. “X”- linked means that the disease is due to a defect in the PHEX gene on the X chromosome and can be passed to offspring. In rare cases, the disease is not inherited from a parent and is due to a new defect in the gene. The PHEX gene is involved in phosphate regulation in the body through the fibroblast growth factor 23 (FGF23) protein. XLH causes there to be an increased level of FGF23. Too much FGF23 prevents the body from retaining enough phosphate and results in low phosphorus levels (hypophosphatemia). Over time, hypophosphatemia leads to soft, weak bones that are more likely to fracture. Bones in the hips, legs, and feet are more prone to fracture which can result in pain and difficulty moving.
XLH can also be referred to as other names including hereditary hypophosphatemic rickets, vitamin-D resistant rickets, or genetic rickets. XLH differs from other types of rickets because it cannot be treated by increasing vitamin D alone.