What Is X-Linked Hypophosphatemia?
X-linked hypophosphatemia (XLH), also called X-Linked Hypophosphatemic Rickets, Familial Hypophosphatemia, Familial Hypophosphatemic Rickets, Vitamin D-Resistant Rickets (VDRR), or Genetic Rickets, is a rare genetic disorder caused by mutations in the PHEX gene. XLH is an X-Linked dominant disorder, which means that the PHEX gene is located on the X chromosome, and people with one PHEX gene mutation will have XLH, even if there are no mutations in the PHEX gene from the other parent. Women with XLH have a 50% chance of passing the condition on to their children. Men with XLH will pass the condition on to all of their daughters, but not to their sons. Sometimes, people with XLH are the first ones in a family to have the condition; in these rare cases, patients did not receive the mutated PHEX gene from a parent but are suffering from a random mutation. However, they can still pass the condition on to their children.
When the PHEX gene is affected by mutations, too much Fibroblast Growth Factor 23 (FGF23) is made in bone cells. FGF23 blocks phosphate re-absorption by the kidney and suppresses the vitamin D dependent phosphate absorption by the intestine resulting in abnormally low levels of phosphate in the blood.
Low phosphate levels in children will lead to poor bone health and a variety of clinical symptoms that may include abnormal bone formation, bone pain, lower than normal bone density, fractures, short stature, tooth abscesses, tinnitus, deformities in the legs (bow or knock-knee), waddling gait, muscle pain and weakness.
Adults with XLH may experience the following symptoms: arthritis; a decreased ability to move; bone, joint and muscle pain; abnormalities where the ligaments and tendons attach to the bone; fractures; and softening of the bones.
The symptoms of XLH tend to appear when a child begins to bear weight on his or her legs. In a very young child (8-16 months), parents may notice bowing and/or twisting of the lower legs, or knock-knees. Teeth may be slow to appear, and the child may be very small for his or her age. Most cases of XLH are diagnosed during childhood; however, the diagnosis is sometimes not made until adulthood because of the variety and severity of XLH symptoms that can occur.
XLH is a rare disease with an estimated prevalence of 3,000 pediatric and 9,000 adult patients in the U.S.
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