Wednesday, April 30, 2014

Dental Manifestations of XLH

Many XLH patients know what it's like to have a spontaneous abscess, when a tooth with no cavities or trauma suddenly becomes infected for no apparent reason. We know it's a common symptom of hypophosphatemia, sometimes happening during childhood and in other cases, waiting until early adulthood.

Some dentists and endodontists, however, may be skeptical about the cause of the abscesses, despite published reports confirming it. [One of the earliest case reports was "Hereditary Hypophosphatemia ... Presenting Primary Dental Manifestations" in Oral Surgery, Oral Medicine and Oral Pathology, volume 22, No. 2 (1966).] If your dentist/endodontist would like to learn more about the connection between your hypophosphatemia and your dental health, there are a number of resources you can refer them to.

For a quick overview, available for free download here, there's "A Clinician's Guide to X-linked hypophosphatemia," (by Scientific Advisory Board member Thomas O. Carpenter, MD, et al.) which briefly mentions dental issues. There's also an oral presentation by our Scientific Advisory Board member, Raghbir Kaur, DMD, in the XLH Day video here (beginning at the 20:30 mark).

If your dentist/endodontist is a member of the International & American Associations for Dental Research, with access to Sage Publications, there's a new article entitled "Rare Bone Diseases and Their Dental, Oral, and Craniofacial Manifestations," in the Journal of Dental Research. The abstract is available here. The article covers a number of rare bone diseases, including XLH, and highlights for each one the causative mutations, etiopathology, and treatments.

Wednesday, April 23, 2014

XLH symptoms ... or not

Today's guest post is by Network member, Andrew Shortall. He was diagnosed with XLH at age two, and has become a self-taught chef, wine businessperson and a writer, with aspirations to become a novelist. 

When living with a chronic illness like XLH, we’re often tempted to associate additional symptoms or conditions with our primary diagnosed complaint. Sometimes, though, it's the doctor who doesn’t fully understand XLH who tries to find a way to tie in the additional symptom.

Back in 2010, I was watching a TV show with a focus on men’s urinary and prostate health. It dealt with things like how to examine one’s own testicles for suspicious lumps, the symptoms of urinary problems and the indicators of a potential prostate complaint. About a month later, I started having occasional pain whilst going to the bathroom, and a week after that, I noticed some blood in my urine. Given this technological age we live in, I went online to the website for the show I had seen. My symptoms seemed to indicate a potential urinary infection or could also possibly indicate a problem with my prostate gland. Being only 34 at the time, I thought I was too young to have a prostate problem.

I checked a little further and found a reliable medical site that seemed bent on trying to convince me I had prostate cancer! Both information sources suggested that it was far more unusual for a man to have a urinary infection, which are more commonly seen among pregnant women. The online advice was that I should immediately increase my intake of water and see a doctor at my earliest chance. I couldn’t get to the doctor until the following Monday, and my symptoms progressed until I was nearly doubled over with pain in the one anatomical element that a man never wants to have pain in!

I made the mistake of going to a health insurance clinic, as my doctor had retired. When I finally got to see a consultant, I was poked, prodded, examined and questioned. He was convinced that my symptoms were linked to the XLH, and that I was potentially looking at the early stages of kidney disease. He seemed puzzled that I didn’t have pain other than when urinating and wondered if I didn’t have kidney stones. I’m no doctor, but I knew for a fact I didn’t. Next came more tests, blood work, urine test, and even an ultrasound of my kidneys.

Since I didn’t have insurance, I had to ask him to stop the testing and just write a prescription for the antibiotics, which cleared up the infection. Even so, my bill was a staggering €550 euro or about $700US. 

I learned quite a few things that day. First, you need to find a doctor well versed in XLH, or at least someone willing to research and listen. Second, online diagnosis tools can’t be your only source of information on medical conditions. Finally, and most importantly, I learned that my kidneys weren’t pregnant!

Wednesday, April 16, 2014

UK patient registry: RUDY

A number of institutions are ramping up their efforts to establish patient registries to facilitate research, and today we're highlighting one such effort in the U.K., with a particular interest in XLH patients.

The UK's National Institute for Health Research (NIHR) has a mission "to maintain a health research system in which the NHS [publicly funded healthcare system] supports outstanding individuals, working in world class facilities, conducting leading edge research focused on the needs of patients and the public."

The NIHR has commissioned a project, known as the Rare UK bone, joint and blood vessel Disease study (RUDY). It's led by a research team at the University of Oxford, and funded by a partnership between the NIHR Rare Diseases Translational Research Collaboration and the Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. At present, the study is limited to UK patients, but they're hoping to develop European collaborations. UK residents will soon be able to visit to learn more or to sign up.

The project was intended to address three problems: rare disorders (like XLH) are under-researched; the information on these disorders, for both patients and doctors, is fragmented; and there is limited reliable data on treatment of these disorders to inform care providers. One of the biggest frustrations for XLH patients is that the symptoms and response to treatment are so variable that treatment involves a great deal of trial and error.

Initially, the project is focused on just six bone disorders, four vascular (blood vessel) disorders, and one other disorder. It may be expanded later to include other conditions. Within the XLH community, the researchers are hoping that the data will provide some clues about the predictors of enthesopathy (the calcification of tendons and ligaments that we're prone to), response to treatment in children, and predictors of non-union fractures. According to the initial documentation, they're looking to learn more about the mechanism of bone pain from patients with another condition that's being studied, fibrous dysplasia, but it wouldn't surprise us XLHers if they also found useful information on the topic from XLH patients.

The project doesn't offer treatment, but collects data on patients, symptoms and treatments. This information will then be available to researchers. For XLH patients, the data may include physical exams, blood and urine samples and bone density scans, as well as collection of past medical records, with lab results and treatment methods.

Obviously, any collection of data is going to raise questions of privacy. Sensitive data will be encrypted and anonymized before it reaches the researchers. Nevertheless, each prospective participant will be well-advised to think about the consequences of sharing information, to read the consent documents carefully, and to decide which pieces of information he or she is willing to share.  The project is set up to allow each participant to decide how much information to release, so it's not an all-or-nothing situation. It's not an easy decision, balancing the individual's privacy with the good for all similarly diagnosed patients that could come out of sharing the information. Obviously, the more data the group can collect, the better the conclusions will be with respect to best practices in patient care.

The project reflects a modern trend toward involving patients – and patient support groups – more directly in the research, helping to guide the research, not just providing the blood and urine samples. The project's leaders are seeking feedback from representatives of the patients in each of the studied group, and this openness to feedback is reflect in the study's motto: "Uniting patients and researchers to investigate rare diseases."

Consistent with that approach, XLH Network Director, Oliver Gardiner, is acting as a liaison between the study and XLH patients in the UK. During an informational session on the project, he met with other liaisons representing patients with Fibrosis Dysplasia,  Osteogenesis Imperfecta (Brittle Bone), Vasculitis  and Lupus. The Genetic Alliance UK was also present, but not representing a particular condition.

Oliver found it uplifting to see so much excitement around the discussion of XLH, and he gained useful insights into how other patient support groups operate. He'll be keeping us up to date on the progress of the study and any useful conclusions that come out of it.

Wednesday, April 9, 2014

Expertise and convenience

Joyce Inman is today's guest blogger. She's the secretary of the XLH Network, Inc., and the parent of a spontaneous XLHer who was diagnosed, as is typical, between her second and third birthdays. 

When our daughter was first diagnosed with a condition that was rare and new to me, we dove into the massive internet searches typical of our Web MD generation. After all the research and discussions with members of the XLH Network, we decided to travel to see a well-known pediatric endocrinologist who specializes in XLH.

I am certain our new doctor must have thought we were slightly insane as we began the process of traveling halfway across the country three times a year to see him; however, we were confident we were receiving the best care possible. Still, at every appointment he suggested that we get a doctor closer to home.  He said he would be happy to work with any doctor we chose, but that eventually we were going to want and need a doctor we could see without getting on a plane.

He was right. The trips for medical care began to take their toll, and my daughter was beginning to resent this additional aspect of her treatment. So, the search for a doctor close to home began again. I started by doing internet searches for pediatric endocrinologists at five different university medical centers within three-and-a-half hours driving distance. At this point, I knew what we wanted in a doctor, and I understood enough about XLH to know what kind of doctor we didn’t want.

During the first search, I'd had no idea that knowing these needs and how to express them would be so valuable. During the early days after diagnosis, I did not know that I needed to look for a doctor with experience treating XLH and who had an active research agenda that would better ensure they were up-to-date in terms of XLH research and treatment. I didn’t know that I wanted a doctor who would be more conservative with the care and would exhaust medicinal therapies before even considering surgery as an option. And because that was the first time I needed a specialist for my child, I did not know what type of doctor personae I needed for our family to feel comfortable with this transition.

During the second search, however, I knew what we needed. I pored over doctor profiles on university websites looking for an endocrinologist who listed interests in endocrine disorders other than diabetes. Eventually, I found a doctor whose research interests included “metabolic bone disorders.” I was cautiously optimistic, but knew that doctors' offices associated with universities tend to be overrun with patients and difficult to get on the phone. So, I emailed the office about our goals in which I explained the following:

  • My daughter’s medical history and our hopes to find a doctor closer to home
  • Our desire to find a doctor willing to work in conjunction with our XLH specialist
  • My hope to have an open relationship with our new doctor in which lab results would be forwarded to me and to our XLH specialist
  • A statement of excitement to have potentially found someone whose research interests suggested an interest in XLH

Two days later we received an email from the local specialist who is now our “home-base” doctor, and she told us she would be happy to meet with us. Our current medical checkups involve seeing our new doctor twice during the school year and a visit to our XLH specialist every summer.

I am posting our story in hopes that it will help provide others with ideas about how to get the best care possible for their children. I am conscious of the fact that many people do not have the option of seeking out medical care that is located outside their city of residence or their insurance network. However, I am also confident that knowing what you need in a doctor, combined with thoughtful correspondence, can lead to strong and rewarding doctor/patient relationships.

My daughter is now seven years old, and we have been working for five years to get to the point that we are now. It has not been easy financially, physically, or emotionally, but it has certainly been worth the peace of mind that comes with finding two doctors who I am confident care greatly for my child and her wellbeing.

Wednesday, April 2, 2014

Meet Pol Harvengt

     This week, we're pleased to have Pol Harvengt here to share a little about his experiences as an XLH patient, a biologist and one of the founders of the patient-support group for French-speaking XLHers. You'll note too that he was one of the named authors of the recently published article, Therapeutic Management of Hypophosphatemic Rickets From Infancy to Adulthood, which can be downloaded for free at

1. How did you get involved with the XLH Network?

When I was young, I was not at all interested in sharing my views on XLH. I had few symptoms and was in a state of denial. Time passed by, I get married and begun to discuss with my wife about founding a family. We consulted an expert geneticist in a famous hospital to get advice on disease transmission and potential severity of symptoms for the awaited child. The geneticist completely misread the literature and get us an overoptimistic picture. When my first child went to birth, we again acted proactively to get the baby blood-tested. Once more, the local padiatrician misread the reference values. Finally, the XLH diagnosis was confirmed a year later. 

The lesson was clear: we needed to identify a really knowledgeable professional to help us. When we finally identified a reliable endocrinologist, my daughter was 2 and was severely bow-legged. With treatment, three years later, the leg bowing was completely gone. 

This experience transformed us, and we felt it was important to share what we learned and to learn from others' experiences. I registered with the XLH Network and from that point, I've continued learning about XLH with great interest. I also realized how important and transformative it is to feel that you are not alone. Recently, I worked with a few other XLHers to found a patient group in France (the first French-speaking one ever) and we have started growing the organization. We hope that we can contribute to a global XLH community.

2. What's your "super power" -- the special skill, knowledge or experience that you bring to our community?

I am a biologist by education. I have a PhD in protein biology and I have worked in biotech research for more than 10 years. I had the opportunity to develop new research tools for a variety of human diseases (cancer, Alzheimer's) as well as new vaccines (Flu, cervical cancer). This gave me the opportunity to learn about human physiology and also to eaasily access scientific literature. Long before most XLH patient learned about new treatments (like KRN23), I had read the scientific reports describing the early discovery and development of these molecules, and even talked to some of the scientists involved in these programs. I was impressed by the kindness and desire to help shown by these brilliant minds. It is a real solace to know that people are out there looking for new ways to help us.

In our French patient organization, I serve as chairman of the Scientific Advisory Board and I am also really delighted to see how far our experts are willing to go to help. This year, our lead French expert will host the first KRN23 clinical trial in Europe, which is also the first XLH clinical trial in more than 30 years in Europe. That is a glimmer of hope and also the first tangible sign that things may change soon for XLHers. And that is probably only the beginning, since a handful of other molecules are moving closer to clinical trial stage. I am convinced we are living in a pivotal time for the disease.    

3. What XLH project are  you working on now that you're particularly enthusiastic about?   
There is so much to do that it is difficult to select one or even a few projects. The initial priorities of the French XLH patient organization were: 1) create a flyer to help local health practitioners correctly diagnose XLH and also for patients to learn how to find experts;  and 2) convince French authorities to get the main phosphate supplement back on the market after the supplier decided to stop production. We've accomplished those goals and are embarking on new projects.

Recently, we had the opportunity to participate in the writing of a scientific review of information about XLH and its treatment. It is published in an open access journal and therefore free to download here. It can help patients access information for themselves or to share with their healthcare provider. That is the kind of project that I would like to develop more in the future, and it is certainly a working model for our organization, with a tight relationship between patients, scientists and also private partners, like biotech companies. Patients should feel empowered to propose scientific projects and should feel like active participants in their health treatment.

With the advent of regional patient organizations, we have the opportunity to build a global XLH community. The language and cultural barriers could still limit the interactions a bit, so I would suggest starting from the scientific model. There is a global language for science, and recent discoveries suggest new avenues to explore and new cures to develop. We will need united efforts from scientists worldwide to succeed.

Finally, I hope that with new therapeutic options like KRN23, we will significantly improve our conditions in the near future. Then I think that we should think about how to help patients in poorer countries that are left with minimal support and treatment options. That would be a formidable challenge and also a noble cause for the global XLH community that is in the making.