Pursuing Elusive Diagnoses for Rare Diseases

Undiagnosed Diseases Program

Laura A. Stokowski, RN, MS; William A. Gahl, MD, PhD


February 26, 2015

Editorial Collaboration

Medscape &

Medscape: How thorough must the evaluation be in the community before the patient would be eligible for acceptance into the program?

Dr Gahl: There is no specific number of referrals or tests. A huge amount of judgment is involved here. We draw from what the consultants in the medical records have written, and we can get a very good flavor of whether they think they have a diagnosis or they really don't know what's going on with the patient. We also have the images and sometimes the biopsies. We put it all together and we ask the question: Is this a common disorder? Have we seen this before, or do we think there is a chance that this is new disorder or a new presentation of a known disorder? With the amount of experience we have, we do a pretty good job of not accepting patients who have a disorder that should be diagnosed. Judgment is really the key here.

Medscape: Do you ever write back and say, "We might take this patient but you need to do these other tests first?"

Dr Gahl: Yes. It's not extremely common but that happens sometimes. We reject 75%-80% of all patients who apply. Of the individuals who are accepted, approximately 10% of them have been asked for more information or more tests to be done before we send the final acceptance letter.

[Editor's note: Genzyme, a Sanofi company, and the National Organization for Rare Disorders (NORD) have created a fund to pay for standard diagnostic testing to help those who have applied to the UDP but who cannot afford the basic medical tests needed to make them eligible for acceptance into the program. For more information, visit NORD.]

Medscape: How long has the average patient been trying to get a diagnosis before they come to you?

Dr Gahl: We don't collect that information in a database but we collect it in our minds. We are not an acute care center. Acute disorders generally don't come to us. These are chronic, undiagnosed diseases. That means that the time that patients have been seeking a diagnosis ranges from 1 to 30 years, with an average of 5-6 years.

Medscape: Some patients aren't accepted directly for the inpatient evaluation at the NIH Clinical Center but instead are referred to other NIH programs. Can you explain how that works?

Dr Gahl: The NIH has the largest collection of experts in rare and unusual diseases in the world. They each have expertise but they also have a protocol, and sometimes the patients who apply to the UDP are eligible for those protocols. There is no reason for them to see us if they are eligible for those protocols, so we just refer them on. Some of these protocols go beyond evaluation and diagnosis and involve treatment for the patients. This might happen, for example, when a patient's data points to a group of disorders that is already being studied by someone else.

Medscape: Is research the primary mission of the UDP? Does the emphasis on research have any bearing on the selection of patients?

Dr Gahl: The primary mission of the NIH is research, but the UDP is unique enough that the NIH gives us purview over our mission. We have two missions. One is to help the patient to come to a diagnosis. The other is research or trying to find out new pathways, targets, and mechanisms of disease and the discovery of new diseases. Research does influence how we select our patients, but we would give as much weight to our ability to make a diagnosis in a very difficult case as we would to our ability to make discoveries in a really good case.


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