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
Has Hearing Loss been associated with XLH?
A more extensive FAQ is available to The XLH Network Inc. members.
Q: What is XLH?
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
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:
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
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
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
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
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
as well as a compilation of some
hearing loss messages
in our mailbag available to our members. A number of
on the topic have also been written by medical professionals.
Carpenter, Thomas O.;
New perspectives on the biology and treatment of X-Linked
Pediatric Clinics of North America 44(2): 443-466 (1997)
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.
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.
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
is available. Please read our full