Mystery disease diagnosed at clinic of last resort

Thanks to the medical detectives at the nation’s first mystery disease clinic, Louise Benge now knows why her legs feel like they’ve turned to stone. 

The 57-year-old Kentucky woman finally has an explanation for the strange disorder that began crippling her â€" and her four siblings â€" nearly three decades ago, making it hard to walk, first a few blocks, then any distance at all.

“Oh, goodness, it’s very hurtful,” said Benge, a retired food stamp clerk from Brodhead, Ky. “Our calves and legs just get as hard as rocks. Sometimes, I just have to stop, period.”

There’s still no treatment or cure for the problem, which also causes severe pain in her hands, Benge acknowledges. But at least there’s a name for the first completely new ailment discovered through the fledgling Undiagnosed Diseases Program begun in 2008 by the National Institutes of Health.

It’s ACDC, or arterial calcification due to deficiency of the protein CD73. Through extensive testing, scientists discovered a genetic glitch that allows bone-like calcium deposits to build up in the blood vessels of victims’ hands and lower limbs. They published their findings earlier this year in the New England Journal of Medicine.

The condition is one of two previously unknown diseases identified through the UDP effort in its first two years. During that time, UPD sleuths also reached diagnoses on at least 39 other patients whose conditions had previously baffled doctors, according to a pilot project review published this fall. That included rare or ultra-rare diseases detected in 28 patients and nine common disorders.

By early this year, the medical detectives had fielded 4,700 inquiries, reviewed 1,700 medical records, rejected 100 cases and accepted 400, with the rest under review, according to a summary by Dr. William A. Gahl, who heads the program, based in Bethesda, Md.

“The discovery of a new disease. That’s something that will stand forever in the scientific realm,” Gahl told TODAY.com.

The program also dramatically expanded knowledge and descriptions of several other disorders in patients who came to what’s now regarded as the clinic of last resort.

“We were tickled,” said Benge, whose condition had stumped half a dozen specialists over several years. “We were just hoping they could figure something out for us.”

Figuring out answers for patients desperate for diagnoses is the goal of the program that started with a budget of $280,000 in 2008 and grew to $3.5 million for 2010 to 2012.

Join other TODAY Health fans -- "like" us on Facebook

“Patients with undiagnosed diseases and their families feel the desperation of uncertainty, the loneliness and isolation of not belonging, and the helplessness of abandonment,” Gahl wrote.

Using sophisticated tools of molecular or biochemical analysis and the out-of-the-box thinking of a team of specialists with time and freedom to pursue any avenue have paid off. There have been dozens of medical triumphs, deducing answers to problems that have eluded others.

In addition to Benge’s diagnosis, the team diagnosed a woman with life-threatening protein deposits in her muscles and a 20-year-old with a previously unknown muscle and lung disorder. Such discoveries inspire deep gratitude, even when no treatment is available, Gahl said.

“They just want some knowledge of what it is, even if it’s terrible,” he noted.

Some patients are still waiting for help, including a young woman with a disorder that prevents her from opening her mouth more than a quarter-inch and a 50-year-old woman who has unexplained spikes of keratin protruding from hair follicles on her scalp.

Others are helping illuminate existing disorders. In the case of Benge and her siblings, the UDP team is using the disease diagnosis to build on knowledge about the relationship between blood vessels and bone formation and to explore new avenues for treating heart disease. They think that a common osteoporosis drug, a bisphosphonate, may help, but are still awaiting clearance to treat patients, Gahl said.

Doctors puzzle over woman's mystery ailment

There’s certainly no shortage of people with diseases that elude diagnosis, Gahl said. In June, the program temporarily stopped accepting applications to allow him and his swamped colleagues to catch their breath.

“We’ve seen so many incredible cases that we really don’t have time to follow up on all of our clues for them,” he said.

Still, starting Dec. 1, Gahl plans to open the floodgates again, mostly because he knows that so many patients like Louise Benge are anxious for answers.

“I hope that it can be fixable, or they can least stop the progression of it,” Benge said. “But we just deal with it and get on with our lives. We were just happy to figure out what was going on and what was causing it.”

Follow @JoNel_Aleccia

Discussion comments

-