A National Institutes of Health (NIH) program aimed at tracking down the causes of mysterious diseases is bearing fruit. A multidisciplinary team of
physicians and genetic researchers have discovered the genetic cause of a bizarre vascular disease afflicting two sisters that leads to a buildup of
calcium in the arterial walls, causing joint hardening and pain.
The group's paper, published in tomorrow's issue of The New England Journal of Medicine, is the first report of a new genetic disease to come out of NIH's 3-year-old Undiagnosed Diseases Program.
It's a consortium of researchers from across NIH and volunteer experts from academic medical centers around the country who receive referrals for
patients whom physicians have been unable to diagnose. "A success like this buoys us emotionally and encourages us," program director and study
co-author William Gahl, who is also clinical director of the National Human Genome Research Institute, said in a press conference Tuesday.
Since its inception in 2008, the Undiagnosed Diseases Program has received 1700 referrals and accepted 330 of them; the researchers report seeing 150
to 200 patients per year. The program's aim, Gahl said, is twofold: to diagnose patients whose diseases have eluded medical knowledge and to conduct
In 2009, the program received a referral from a Kentucky doctor for two sisters, Paula Allen and Louise Benge, who suffered from joint pain and showed
calcium buildup in their arteries in x-rays (above). The images "astounded us," Gahl said. The team obtained DNA samples from the sisters and other family
members (three of Allen and Benge's siblings had the same recessive disease) and scanned the DNA for markers called single nucleotide polymorphisms
that the researchers used to narrow the location of the disease gene. By also examining this genetic region in two other families with similar
disorders, the researchers were able to pinpoint a mutation in a specific gene, NT5E, which is involved in breaking down calcification in the
The researchers named the disease ACDC (arterial calcification due to CD73 deficiency). The discovery revealed a previously unknown molecular mechanism
for preventing calcification and may open treatment avenues for patients suffering from the more common diseases of atherosclerosis and osteoporosis,
said study senior author Manfred Boehm of NIH.
Allen and Benge praised the "impressive" work by NIH. "Even if they can't help us, maybe someday they can help someone else with these problems," said
Benge. Boehm said that a clinical trial for a drug to treat the sisters and others with ACDC is currently under review by an ethics board.
The undiagnosed diseases program is "wonderful; ... we were thrilled when it started," said Mary Dunkle, spokesperson for the National Organization for
Rare Diseases (NORD), a Washington, D.C.-based patient advocacy group. NORD has referred a number of patients to NIH. "In our world, a lot of times
knowledge is gained in small increments," Dunkle said. "It's always progress when they're able to identify something that's a complete new entity."
*This item has been corrected 4 February to reflect that study co-author William Gahl is also the clinical director of the National Human Genome Research Institute.