Some 500 diseases are common enough that any physician can diagnose them. Another 6,500 are known but exceptionally rare, each affecting fewer than 10,000 Americans, according to the NIH Office of Rare Diseases Research. When you add up every American with a rare disease, though, the total is nearly 30 million, or one in 10, says Mary Dunkle, vice president of communications at the National Organization for Rare Disorders, an advocacy group based in Danbury, Conn.
Because rare diseases can affect multiple organ systems, patients often have no idea what type of doctor they should turn to first, Dunkle says. “Or they get told it’s all in their head. Even their own families think they’re just being hypersensitive and imagining things.”
Before the UDP, “these people had no hope at all,” she says. “The concept of getting physicians from different specialty areas to work together as a team and look at these diseases makes so much sense.”
The UDP might bring TV’s House to mind, but the reality bears little resemblance to the detective work performed at the fictional Princeton-Plainsboro Teaching Hospital in New Jersey. Dr. Gregory House is a one-man diagnostic band, assisted mainly by young residents. In the UDP, elite specialists from the 27 institutes that make up NIH can consult on cases when needed. While House and company “deal with largely acute disorders, our disorders are largely chronic,” Gahl says.
And unlike House, Gahl and company don’t wrap up all their cases quickly and decisively. The second paragraph of the UDP acceptance letter states directly: “Not all admissions will result in a diagnosis.”
Of those first 160 UDP patients seen at the Clinical Center, only 39 received diagnoses. Some were new variations of known diseases, but a small number were new. The program made headlines around the world in February 2011, when it reported its first new disease in the prestigious New England Journal of Medicine. Gahl’s team dubbed the previously unknown genetic disorder “ACDC,” not for the hard-rock band, but for “arterial calcification due to deficiency of CD73,” a protein.
Sisters Louise Benge, now 57, and Paula Allen, now 52, came to the UDP from tiny Brodhead, Ky. Their X-rays showed a buildup of calcium in the large blood vessels of their hips, legs and hands, a painful condition that they and their siblings had endured for 20 to 30 years. At a press conference announcing the sisters’ newly identified disorder, Gahl said he was “astounded” when he saw the X-rays, because the women had calcification where it normally doesn’t occur.
A key factor in reaching a diagnosis was the fact that the sisters’ parents, who don’t have the disorder, and other family members could provide tissue samples for genetic testing, Gahl says. The sisters were found to have a mutation in both copies of a particular gene; their parents, who were third cousins, had a mutation in only one. Apparently the parents each passed a mutated copy to their daughters, resulting in ACDC.
Since the diagnosis, NIH researchers have received approval to test drugs called bisphosphonates to treat the disease. They’re already on the market for the treatment of osteoporosis, and studies have suggested that bisphosphonates can regulate the accumulation of calcium in arteries. UDP scientists hope what they learn about treating ACDC can be applied to patients with atherosclerosis, since calcification in the coronary arteries has been linked to a greater risk of heart attack.
Benge and Allen are atypical of UDP patients in that they received both a diagnosis and a potential treatment. “I come in early in the week to tell folks we don’t have the best track record and we usually fail,” Gahl says. “I think that some of them are indeed disappointed.”
Just because they leave Bethesda without a diagnosis doesn’t mean their case is closed, however. UDP doctors will continue to look for patients with similar symptoms. “You remember the patients because they’re so challenging, and they’re so different,” Gochuico says.
Although patients must be well enough to fly a commercial airliner to Washington, perhaps 20 have died either before making it to the NIH center or shortly after, Gahl says. “Some of these folks, we know they’re going to die in the next few years, especially the kids. Some of them are in bed all the time, in a wheelchair. They can’t feed themselves. Some of the adults who have late-onset neurological disease are also going downhill.”
Many patients will say, “ ‘I know you may not be able to help me because it’s too late, but I want to help other patients,’ ” Gahl says. “It’s sort of depressing how desperate the human condition is sometimes.”