Pursuing Elusive Diagnoses for Rare Diseases

Editor's Note: There are no published statistics on the number of undiagnosed "rare disease" patients currently in the United States. The accepted definition of a rare disease is one that affects fewer than 200,000 Americans at any given time. According to the National Institutes of Health (NIH), there are between 6000 and 7000 rare diseases affecting from 25 to 30 million Americans, making it likely that most, if not all, healthcare professionals have these patients in their practice. The average time to diagnosis for a rare disease is about 7.2 years. Patients with disorders of unknown etiology (undiagnosed rare disease patients) sometimes never receive a diagnosis or appropriate treatment.

The Undiagnosed Diseases Program (UDP) originated as a program of the National Human Genome Research Institute (NHGRI), the NIH Office of Rare Diseases Research (ORDR), and the NIH Clinical Center, and launched in 2008 at the NIH campus in Bethesda. It was designed to leverage the NIH's expert staff and cutting-edge research tools to diagnose rare diseases in patients who have signs and symptoms that have eluded a definitive diagnosis.^[1] A second goal of the UDP is to advance knowledge of rare diseases and new presentations of common diseases.

In its first 6 years, the UDP has enrolled more than 800 undiagnosed children and adults in its clinical protocols. In addition to providing partial or complete diagnoses for up to 40% of those evaluated, the program's multidisciplinary team of experts has discovered two unknown diseases and identified 15 genes not previously known to be associated with any other human disease. However, the UDP has been able to accept only a fraction of the patients who apply to the program—over 10,000 inquiries to date. The popularity of the UDP has demonstrated that a substantial unmet need exists for intensive evaluation of undiagnosed diseases among the population. Therefore, an extension of the program is underway that will add six new clinical sites at Baylor College of Medicine; Harvard teaching hospitals (including Boston Children's Hospital, Brigham and Women's Hospital, and Massachusetts General Hospital); Duke University; Stanford University; University of California, Los Angeles; and Vanderbilt University Medical Center.

Medscape had the opportunity to speak with William A. Gahl, MD, PhD, clinical director at the NHGRI and director of the UDP, about the program's successes and challenges, and what clinicians should know about the UDP and how it may be able to help patients in their practices who have chronic, undiagnosed diseases.

Interview With Dr William Gahl

Medscape: What is an undiagnosed disease?

William A. Gahl, MD, PhD

Dr Gahl: If a patient doesn't have a fairly definitive diagnosis after having gone through a tertiary medical care center, then that patient's disease would be undiagnosed. Practically all of the patients whom we have seen carry a diagnosis that has been given to them, even if it's incorrect, uncertain, or incomplete, and even though the doctors in general know that it's incorrect or incomplete. Our patients have too many diagnoses rather than not enough diagnoses. Sometimes physicians write down a diagnosis for purposes of reimbursement, but it isn't definitive. A patient who has gone to a tertiary medical care center and seen specialists, but still does not have a diagnosis, would be one way to look at the definition.

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