NIH MedlinePlus magazine talks with mystery-disease detective Dr. William Gahl, Director of the NIH Undiagnosed Diseases Program
What kind of emotional support does your program offer patients?
For some, real hope and maybe even relief. As doctors, we feel deep compassion for patients who have been without hope because they are sick and no one has been able to help them. A principal mission, however, is the discovery of new diseases and variations of known diseases.
Have your insights and research been able to help?
For some patients, we not only make a diagnosis but also can provide treatment or refer them elsewhere. But even when there is no treatment, simply having our diagnosis can be helpful. Many patients would rather know they have a fatal disease than go on with the uncertainty. Uncertainty is the major issue.
Could you describe one of your cases?
We diagnosed a woman whose muscles had grown so much in the previous 10 years that people wondered whether she was training as a bodybuilder or was on steroids. But most exercise was painful, and eventually her muscle mass grew so heavy that she felt exhausted all the time. We diagnosed a potentially fatal protein buildup in the skeletal muscles. Once that was made—and it was made solely because of this program—she got a stem-cell transplant at the Mayo Clinic in Rochester, Minn., and is now recovering.
What does a patient find with NIH that she may not find at another hospital?
First, we provide patients with coordinated access to many specialists. Second, different consultants can meet to discuss a given patient at the same time. Third, we offer state-of-the-art genetic analysis. Fourth, we plan to expand our basic research into the disorders we are seeing.
Is there a unique part that genetics plays in the UDP?
Yes. Before coming here, our patients have gotten the standardized genetic tests that largely focus on a particular symptom. We consider those tests as a starting point.
Can you give an example of how genetics has been applied?
Yes. We just discovered a new disease we’ve named ACDC. In nine individuals from three different families around the world, we found that a mutation in a gene called NT5E is inhibiting production of adenosine, which the body’s large blood vessels need to avoid calcification. The large vessels of their bodies are calcifying, mostly below their waists, but the calcification also involves the joints of the hands and feet, making movement extremely painful.
Are there any possible implications for other, more common disorders?
We won’t really know how significant this discovery is for years. It could have all sorts of applications, including in the normal calcification of bone, and, possibly, abnormal calcification in other places, such as the blood vessels. But it’s also possible it could only have implications for the affected family members we’ve studied. But knowing that adenosine has these functions is critically important for both basic and clinical research.
Have you cured the people you were studying?
Although there may be some healing, our treatment probably won’t reverse the calcification in our patients. Mainly, we want to avoid possible amputation. One person already has had to have an operation to bypass the femoral artery in the leg, so it’s pretty serious stuff.
Have you ever dealt with so many varied cases?
I’m not sure anybody deals with the diversity of cases that UDP does. We’ll see anyone about anything as long as we have someone around here who knows a little bit about it. Even when we don’t have the expertise, we do have the genetics. The good part is that we are helping people who wouldn’t have been helped otherwise.
Have you met your expectations for making diagnoses?
Yes. We have diagnosed 15 or 20 percent of the patients we admitted, which is a little more than we expected. We believe we’ll be able to diagnose more as more basic research is performed.