WEDNESDAY, Oct. 26 (HealthDay News) -- A sibling pair with a puzzling condition that made even walking a short distance an agony; a 20-year-old man with a rare respiratory ailment forcing him to live on a ventilator; a woman with a potentially fatal buildup of a protein in her muscles -- all rare cases that were difficult to diagnose, let alone treat.

And yet all of these patients, and dozens more, have had their "mystery" illnesses properly diagnosed and, in some cases, treated, through work done at a "clinic of last resort" run by the U.S. National Institutes of Health (NIH).

Researchers at the NIH's Undiagnosed Diseases Program (UDP) in Bethesda, Md., say that since the program's inception two years back, they've made considerable headway in unraveling complex medical riddles like these that have puzzled patients and physicians alike.

"We're talking about patients who have gone a long, long time without any diagnosis," noted UDP director Dr. William A. Gahl, who is also clinical director of the National Human Genome Research Institute (NHGRI). "These are patients who have already been seen at one of the country's major health facilities -- sometimes all of them -- but have had no success."

Established in 2008, the UDP has taken on the cases of 326 patients out of a pool of nearly 1,200 applicants.

Of these, 39 have gone on to see their cases "solved." This, Gahl and his colleagues explain, means that after an exhaustive investigation, doctors have reached a definitive diagnosis.

The program's access to cutting-edge genetics technologies has been key to its success, Gahl said. "[We] offer something others can't: greater in-depth in-patient access to first-generation genetics on a wide scale," he said.

Writing in a recent issue of Genetics in Medicine, Gahl and his colleagues detailed the UDP's objectives and achievements to date, describing the experiences of 160 patients who have already participated in the program.

Some examples:

• A pair of siblings who developed a buildup of calcium deposits in their arteries that rendered even walking painful. Investigating their case, the UDP team pinpointed a deficiency in a protein that would otherwise keep arteries from calcifying. Reported in the New England Journal of Medicine, it was the program's first discovery of a new disease. It's thought that a particular drug protocol might help these patients.
• A woman who suffered a buildup of protein in muscle tissue, which turned out to be a rare form of a bone marrow disease called amylodosis. A stem-cell bone marrow transplant has subsequently brought about steady improvement in her condition.
• A young man with a mysterious lung/muscle ailment that forced him to use a ventilator daily. The UDP team pinpointed the illness as "spinal muscular atrophy with respiratory distress," and eased his concern that it might somehow impair learning. At 20 years of age, he is now the oldest known survivor of this rare disease.

Gahl and his colleagues point out that a center like the UDP is crucial for patients like these, because the typical physician will only be knowledgeable about roughly 500 common diseases.

On the other hand, about 6,500 rare (and unfamiliar) illnesses are known to exist. "Rare diseases" are defined are those that strike fewer than 200,000 Americans. They often occur in the absence of reliable diagnostic tests or clear clinical definitions.

Trickier still are the so-called "extremely rare" diseases, those affecting fewer than 10,000 patients. And then there are the wholly unknown illnesses: new diseases that have yet to yet to be identified and named.

Patients admitted to the UDP first undergo a battery of evaluations and genetic tests, often along with family members.

"We see two to four patients every week, and every one is really a mystery," noted Gahl. "But with the UDP we are able to do the kind of testing in one week that would ordinarily take one or two years."

More than half of the 160 patients (65 men, 95 women) highlighted in the current UDP report entered the program with an undiagnosed neurological issue. Other symptoms appeared to stem from a variety of causes, such as heart disease, skin disease, mental illness, pain, gastrointestinal disease, fibromyalgia and chronic fatigue syndrome, autoimmune disorders and rheumatic illnesses.

In many cases, researchers work with DNA, blood, urine and other variables long after a patient departs the center. According to Gahl, it can take a year or two of "devoted effort" to decode a single illness. And there's never any guarantee of success.

That's why, "we try to select individuals and families that we feel we can help," according to UDP senior staff clinician Dr. David Adams. "By that I mean that if someone has a condition with the hallmarks of a genetic condition as opposed to something caused by an individual's environment, then it's more likely that the genetic tools we have to use are going to be useful."

But he stressed that, "even with a diagnosis, it's unlikely you will be able to come up with a treatment that will help that particular patient. These are patients that have already undergone a huge medical odyssey even before they come to us, and by this point it's not likely that they will be fixed by some 'miracle cure' based on our work."

"Our diagnosis rate is about 20 percent," Adams said, "and we have had a few cases where we've been able to help an individual. But we know that in many cases that's not going to happen. And so a lot of what we're trying to accomplish with this program is longer term. To contribute to medicine, so that an ultra-rare disease or syndrome becomes better diagnosed and more easily treatable."

Of the program's 39 "solved" cases to date, 15 involved men and 24 involved women. Eight of the cases have been deemed "rare", and 15 "extremely rare". Two turned out to be new, never-before diagnosed illnesses.

"That's the part that's intellectually satisfying," Adams said. "Where we're thrilled to have the opportunity to figure out what's really going on. But then on the other hand, as a practicing physician, some of the cases are just heartbreaking. We're working with devastated families, who know they're being helpful, but who we know we probably can't treat, much less cure."

"It's a balancing act we try and strike every day."

More information

Find out more at the U.S. National Institutes of Health, Office of Rar...iseases Research.