FAQ: Frequently Asked Questions About XLH

What is XLH?
Is there a single mutation responsible for XLH?
Does XLH affect everyone the same?
How do people get XLH?
Is XLH curable?
Is XLH Treatable?
How is XLH-Rickets different from other forms of Rickets?
How common is XLH?
How is XLH diagnosed?
Is there a genetic test for XLH?
How do I find a specialist who has experience with XLH?
Can XLH patients participate in athletic activities?
Are there dental problems associated with XLH?
Has research been done using Human Growth Hormone for XLH patients?
Has Hearing Loss been associated with XLH?

A more extensive FAQ is available to The XLH Network Inc. members.

Q: What is XLH?
A: X-chromosome Linked Hypophosphatemia is a metabolic disorder with a genetic basis, that usually results in bowed or bent legs in growing children. In XLH, the mechanisms that control the body's ability to make and maintain bones (and teeth) do not work correctly. One of the things needed for good bone growth is the mineral phosphorus. The key characteristic of XLH -- low phosphorus in the blood, also known as hypophosphatemia -- is the result of a mutation (change) in one of the genes on the X chromosome. When this gene, called the PHEX gene, has the XLH mutation, bone cells are unable to produce an enzyme which is a crucial cog in the biochemical machinery that maintains the blood's proper level of phosphorus. This system is still not fully understood but it is under intense investigation by the medical research community.

Q: Is there a single mutation responsible for XLH?
A: So far, approximately one 175 different mutations in a particular section of the X chromosome have been identified for XLH. Scientists update a database of each of the possible mutations as each one is discovered. An XLH patient might have one of these mutations, or a new one that has not yet been described. People are often unaware that everyone in the world has about 10 different mutations in their own genetic code. Often these mutations have no apparent effect; but sometimes, as in the case of XLH, their effects can be significant. A database of XLH mutations is available here: http://www.phexdb.mcgill.ca/

Q: Does XLH affect everyone the same?
A: Yes, and No. Everyone with XLH has low phosphorus in the blood; but the severity of bone symptoms can vary widely between individuals who have XLH, even in the same family. A minimum or 5% of people [Winters, 1958] with XLH do not even show any bone symptoms, but only have low levels of phosphorus in their blood. The reasons for these differences are not yet understood.

Q. How do people get XLH?
A: XLH is a genetic disorder. Approximately one third of subscribers to the mailing list for The XLH Network Inc. have XLH without any apparent family history, and are considered to be spontaneous cases. In the other two thirds of the subscribers, XLH is inherited from a parent known to have the syndrome. The condition is X-Linked and dominant. This means that the gene responsible for XLH is on the X chromosome and if a person has the mutated gene, they have XLH.

Men have one X and one Y chromosome, whereas women have two X chromosomes. Daughters receive either of their mother's X chromosomes and they get their other X chromosome from their father. Sons get either of their mother's X chromosomes and their father's Y chromosome. Therefore, all female children of an affected man would inherit the condition because he has only the affected X to pass along to them, but none of his sons could inherit XLH because they would receive only the Y chromosome from him. Every child of an affected mother has a 50-50 chance of inheriting XLH, dependent on whether they receive the affected or the unaffected X chromosome from her. If the syndrome is present, regardless of whether it is a spontaneous case or inherited from an individual's parents, that individual will have the same likelihood of passing on the condition to their children.

Q. Is XLH curable?
A: No. The best medical science can offer today is treatment that ttempts to correct the symptoms of XLH. The gene that carries the XLH mutation has already been identified. Scientific research is particularly intensive, at the moment, to try to understand how the affected gene works in the control of phosphorus levels in the blood. Gene therapy, in which the defective gene is fixed, holds longer-term promise. There are important advances in research going on right now, and The XLH Network Inc. is actively informed by some of the world's leading researchers, but it will likely be several years before some of these new research directions bear fruit.

Q. Is XLH treatable?
A: The treatments currently available can help in many but not in all cases. Often, a combination of a particularly active Vitamin D, together with phosphorus supplements, is prescribed in oral form in an attempt to achieve a better balance of phosphate, calcium and crucial hormones. This treatment may have limited effectiveness and also potential side effects, requiring periodic monitoring throughout the patient's life. Because of the variability of symptoms, each case is unique and must be treated individually. In general, however, the earlier the diagnosis can be confirmed and therapy started, the better the results may be. In some cases treatment continues throughout the patient's lifetime. The crucial time for treatment is during a children's growth years, in order to help their legs to grow straight. Many children who begin treatment with very bowed or bent legs, mature into adults with straight lower limbs. Sometimes orthopedic surgery is required to correct badly deformed legs, but often specialists expect to see good progress with the medication, minimizing the need for surgery.
The debate of whether treatment should continue after adulthood is described in an article by Dr. Whyte's at Shriner's page on " It's Called XLH." in which Dr. White says in "Once their bones are straight and have stopped growing, Whyte said, it seems that the drug therapy can be stopped with little fear of deformity returning." Yet, he writes "If inadequately treated in childhood, a middle-aged XLH sufferer often experiences painful cracks in bones, osteoarthritis reflecting premature wear in the knees and hips, and calcification in the membranes around the joints and between bones."

Q. How is XLH Rickets different from other forms of Rickets?
A: At the end of the 19th century, many children had rickets because they didn't get enough Vitamin D in their diet or have sufficient exposure to sunshine. Sunshine helps our bodies to make Vitamin D. Today this kind of rickets, while uncommon, is still found when sunlight exposure or dietary sources of Vitamin D are in short supply. For people affected by XLH, no matter how much Vitamin D is provided in their diet or through the sunshine's effects, rickets does not improve. This is the reason for one of the early names for XLH: Vitamin D-RESISTANT rickets.

Different kinds of genetic rickets have been discovered recently, but XLH is still the most common form of rickets that can be inherited. These conditions are similar in that in each the metabolic processes necessary for proper bone formation are affected. Each of the different forms of rickets provides a unique insight into the linkages between genes and bones, and each condition has been invaluable in improving our basic understanding of the process of bone formation and maintenance.

Q: How common is XLH?
A: When XLH is present in your family, it is common indeed! Members of the XLH Network Inc. are often part of extended families in which several family members are affected. In terms of the general population, it is estimated that there is one person with XLH for every 20,000 who do not have this syndrome. It is a rare disorder. But when it is you who is affected, the incidence is 1 in 1. That's why the XLH Network Inc. is so important to its members. Each of the people in the network is affected in one way or another by XLH, and we each share some of the experiences involved in this syndrome.

Q: How is XLH diagnosed?
A: XLH patients have low phosphorus in the blood (hypophosphatemia) which can be detected with a simple blood test typically performed in a clinical chemistry laboratory, though blood samples can be drawn in a doctor's office. This is the most convenient way to test for XLH when there is a known family history. Members of The XLH Network Inc. know that the normal values for phosphorus levels in the blood are dramatically different in children than in adults, but for some reason clinical chemistry laboratories do not always report normal age-matched levels to the physician requesting the test! This can sometimes lead to a missed early diagnosis. If there is no family history, more exhaustive tests will probably be needed to rule out other possible causes of rickets symptoms. The time spent trying to reach a diagnosis in these cases can be frustrating for both parents and the child's doctor! Specialty care is, however, very important in both the diagnosis and treatment phases of XLH.

Rickets can often also be identified using X-rays. Lower leg bowing can be obvious. Additionally, to a trained eye, X-rays can provide clear evidence of what are called rickets lesions, even before the leg begins to bow. Parents may notice early bowing problems when their child begins to walk. Increasingly, dental problems, especially numerous spontaneous tooth abscesses and enlarged pulp chambers, are recognized as a common ailment of XLH. Other possible symptoms are bone pain, as well as muscle pain and weakness.

Q: Is there a genetic test for XLH?
A: Yes. A genetic test for XLH and two other forms of genetic rickets became available in March 2001. A detailed analysis of the issues involved with genetic testing with specific reference to this genetic test, is available in the Members Web Space of The XLH Network Inc., available to memebrs of The XLH Network Inc.

Q: How do I find a specialist who has experience with XLH?
A: It's essential to have a physician well-versed in the management of XLH following the patient. Most often an endocrinologist or nephrologist with a special interest in metabolic bone diseases will be the specialist that patients will see. These specialist physicians are found in major medical centers and teaching hospitals since they will generally be the ones keeping most up-to-date on rare conditions such as XLH. One of the benefits of joining The XLH Network Inc. is that members help new patients find experienced medical specialists.

Q: Can XLH patients participate in athletic activities?
A: Many people affected by XLH can lead active lives and participate in sports and athletics without harm to their bones. Healthy bones and exercise go together. The FDA has published an article on the role of diet and exercise on growing bones, and many of the suggestions are as valuable for people with XLH as for those who do not have this syndrome. However, is important for XLH patients, especially in their growing years (under 18), to be under the care of a medical professional who can monitor bone growth, maintain appropriate medication, and advise on the appropriateness of any particular exercise.

Q: Are there dental problems associated with XLH?
A: Yes. Problems with the formation of teeth can result in dental abscesses. These dental abscesses are not the result of poor dental hygiene, but have their basis in improper formation of dentin and other tooth structures. Like bone problems, these problems are also vary from patient to patient. Detailed information on dental problems associated with XLH is available to members in the Members Web Space.

Q: Has research been done using Human Growth Hormone for XLH patients?
A: For the last several years, medical researchers have studied Human Growth Hormone as a way to increase stature of XLH patients during their growth years. There exists extensive published research on this topic. While there have been encouraging results with some patients, there does not yet exist a medical consensus for this treatment option for XLH. A summary of current research is available to XLH Network Members.

Q: Has Hearing Loss been associated with XLH?
A: Yes it has. Some XLH patients have hearing loss which progressively increases in severity with age. The severity varies from patient to patient as does the percentage of patients who have hearing loss which can be attributed to XLH. Hearing loss varies significantly between different people based upon a number of factors, including prolonged exposure to loud noises, ear infections and a host of other factors. For this reason, it is often difficult to attribute specific hearing loss to XLH. We have had a number of member discussions available in our archives as well as a compilation of some hearing loss messages in our mailbag available to our members. A number of medical abstracts on the topic have also been written by medical professionals.

Abstracts

Carpenter, Thomas O.; New perspectives on the biology and treatment of X-Linked Hypophosphatemic rickets .; Pediatric Clinics of North America 44(2): 443-466 (1997)
PubMed ID: 9130929

Robert W. Winters, John B. Graham, T. Franklin Williams, Vernon W. McFalls and Charles H. Burnett. A genetic study of familial hypophosphatemia and Vitamin D resistant rickets with a review of the literature. 1958. Medicine:37:97-142.

Last modified Mar 27, 2011

XLH is also known as X-Linked Hypophosphatemia (sometimes also spelled as hypophosphataemia), X-Linked Hypophosphatemic Rickets, Familial Hypophosphatemia, Vitamin D-Resistant Rickets (VDRR) Rickets and even Genetic Rickets. Its notable characteristics are bowed legs, short stature, poor teeth formation causing spontaneous dental abscesses, and low blood phosphorus levels.

© 2002-2011, The XLH Network Inc.
The authors of this web site are not medical professionals, and this information does not substitute for medical care. Information on these pages is based on biomedical research, published in peer-reviewed journals, and international research conferences. Additionally, in some cases anecdotal information is provided by subscribers of the F-HYPDRR group, a mailing list for The XLH Network Inc. A complete web-site bibliography is available. Please read our full disclaimer.