What Is X-Linked Hypophosphatemia?
A SURVEY OF XLH PATIENTS IS BEING CONDUCTED. CLICK FOR MORE INFO
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.
This confidential survey asks you questions about your/your child's experience with XLH, including family history, diagnosis, medical conditions or symptoms, surguries received, medications taken for XLH, and how XLH affects your/your child's daily life. The information gathered from this research study could be used to increase awareness of the disease and could encourage additional research and development.
If you're not sure about an answer, please give the best answer you can.
Please note: This survey will take about 45 minutes to complete. Please make sure you have enough time to think about and answer each questoins thoroughly.
**You must be 18 years or older to complete this questionnaire. If you are under 18, a parent/guardian/caregiver must complete this survey on your behalf.
Click here to complete the survey.
The current standard of care for most pediatric patients with XLH includes using oral phosphate replacement and vitamin D therapy. This therapy requires close monitoring by the physician and high compliance from the patient, due to the risk of phosphate levels getting too high, which can result in damage to the kidneys and parathyroid glands.
The standard of care for adults is less well established.
Ultragenyx is collaborating with Kyowa Hakko Kirin Co., Ltd. (KHK) to develop KRN23, an investigational product, for XLH in children and adults. KRN23 is a fully human monoclonal antibody discovered by KHK and administered by injection under the skin. In XLH, the underlying cause of disease is an excess of FGF23. KRN23, an antibody, is designed to specifically target FGF23, bind to it, and reduce FGF23 activity. The goal of therapy is to increase abnormally low phosphate levels and enable patients with XLH to make their own vitamin D. Increased phosphate levels could improve bone health and therefore prevent or heal rickets in children and potentially improve osteomalacia in adults and reduce the associated symptoms of the disease.
If you are a member of an XLH patient organization and would like to be listed here, please contact us.
Ultragenyx is collaborating with Kyowa Hakko Kirin Co., Ltd. to develop KRN23, an investigational product, for XLH in children and adults.
Ultragenyx is leading a Phase 2 clinical study of KRN23 in children ages 5 to 12 with XLH. For more information about this study, please visit the study page.
A Phase 2b study in adults with XLH is ongoing and a Phase 3 program is scheduled to begin in the second half of 2015.