2011 Science, Technology and Environment

William A. Gahl

Brings together medical specialists to diagnose mysterious diseases for desperate and long suffering patients.

As the founding director of the Undiagnosed Diseases Program at the National Institutes of Health (NIH), Gahl has brought together a unique combination of elite medical specialists, researchers and federal resources to solve baffling illnesses and provide desperate patients with information and possible solutions for their often life-threatening ailments.

Results include successful diagnosis and treatment of diseases so rare that they don’t even have names, plus new genetic discoveries, improved disease management and the advancement of medical knowledge.

Dr. Francis Collins, the director of NIH, said the program was conceived and started by Gahl, and serves as a kind of “court of last resort” for patients without a diagnosis. He said Gahl convinced some of the best, brightest and busiest physicians to participate, and has devoted tremendous energy to examining patient records, selecting cases for in-depth analysis and helping people who are seriously ill.

“It’s a testament to his effectiveness as a leader,” said Collins. “This was his vision.”

Under Gahl’s stewardship, the program regularly involves a collective effort by more than 25 attending physicians whose specialties include neurology, internal medicine, pediatrics, endocrinology, immunology, dermatology, pulmonology, cardiology and genetics. The cooperation by a diverse group of experts has helped create a coherent view of each patient instead of the typical organ-by-organ orientation taken by most specialists.

Patients are brought to the NIH campus in Bethesda, Md., for an intensive week. They meet with a parade of specialists who study their medical histories, perform thorough examinations and take numerous tests. The doctors then meet to discuss what they have seen, discovered or may have missed. They also debate various theories, try to connect the dots and come up with possible diagnoses and treatments.

Since its inception in May 2008, Gahl and his staff have received more than 5,000 inquiries, reviewed more than 1,800 cases, and after consideration by a medical review board, accepted about 400 individuals whose unique conditions have confounded experts. So far, a medical diagnosis has been found for about 60 of the individuals.

Dr. Eric Green, the director of the National Human Genome Research Institute, said the success rate is not high because of the complexity and unusual nature of the cases, but he emphasized that there have been significant benefits for many individuals who have been “abandoned by the medical system.”

Earlier this year, scientists working with Gahl discovered the genetic cause of a vascular disorder not previously identified in the medical literature. The rare condition, identified in nine individuals, arises in adulthood and causes arterial calcification in the hands and feet, but does not affect arteries in the heart. The symptoms include pain on walking more than a couple of blocks.

Collins said the disorder “previously baffled the medical field and evaded diagnosis when conventional methods were used.”

In another instance, the physicians working with Gahl identified the reason why a woman’s muscles had grown painfully large and hard underneath her skin, making it increasingly difficult for her to perform daily activities. This turned out to be an extremely rare, generally fatal complication of multiple myeloma, and the diagnosis by the NIH Undiagnosed Diseases Program resulted in a stem cell bone marrow transplant that allows her to lead a normal life.

The program also has dealt with many heartbreaking and unsolvable cases, including that of a woman who over many years suffered multiple system breakdowns. These included kidney failure, intestinal bleeding, seizures, osteoporosis, bone-tissue death in both legs, and the loss of an eye. The 31-year-old woman died some months after visiting NIH.

Gahl, who has made a number of seminal discoveries regarding rare diseases during his career, said that deciding who to admit into the program is always very difficult and much like triage on the battlefield. “You have to make a decision about whether you think you can do something,” he said.

Gahl said the program serves people who feel helpless, have suffered greatly, have waited many years for answers, and must be treated with “respect and attention.” He said the NIH caregivers understand the desperation felt by the patients and try to balance the difficulty finding solutions with “a realistic measure of hope.”

“The patients appreciate the attention paid to their condition and the hope that accompanies that attention,” he said.

Dr. John Gallin, director of the NIH Clinical Center, said Gahl takes cases “after everybody else has given up,” and devotes enormous resources that are not ordinarily available to patients.

He said the program in a short time has developed new approaches for investigating, understanding and diagnosing rare disorders, and has added to the body of medical knowledge.

“As a result of the NIH Undiagnosed Diseases Program, the language of medicine is changing,’ said Gallin. “The different specialists working together now are beginning to think in common ways.”