Medical Detectives New Disease

Ms. Benge’s family doctor in Mount Vernon, Ky., was at a loss, as were a vascular specialist, a hand specialist and a kidney specialist. Her two sisters and two brothers had the problem too, but no doctor could figure out why.

It was clear from X-rays why Ms. Benge could barely walk: The blood vessels in her legs, feet and hands were accumulating calcium deposits like the scale that sometimes forms inside water pipes. The deposits had grown so thick that blood could hardly squeeze through. But calcium was only in those blood vessels of her legs and hands; her heart’s vessels were spared, so she was not in immediate danger of dying.

A doctor prescribed weekly infusions of a drug, sodium thiosulfate, Ms. Benge said, thinking it might bind to the calcium so her body could flush it out. But the drug did not work — it only made her vomit.

Finally, Ms. Benge’s family doctor sent her medical history to a detective agency of sorts, the Undiagnosed Diseases Program at the National Institutes of Health. Set up in the spring of 2008, the program relies on teams of specialists who use the most advanced tools of medicine and genomics to try to figure out the causes of diseases that have baffled doctors.

The idea was that understanding rare diseases can give insights into more common ones, said Dr. William A. Gahl, director of the program.

And, he said, there was another reason.

“Patients who have rare diseases are often abandoned by the medical community,” Dr. Gahl said. “We don’t know how to treat if we don’t have a diagnosis. The way our society treats abandoned individuals is a measure of our society. It speaks to how our society treats the poorest among us.”

With Ms. Benge and her siblings, the researchers have their first newly discovered disease. It is caused, they report on Thursday in The New England Journal of Medicine, by a mutation in a gene that prevents calcium from depositing in blood vessels.

Now that they know the cause of the disease, the researchers have ideas for how to treat it. And the discovery also has implications for more common diseases, like heart disease and osteoporosis, in which calcium is deposited inappropriately.

The unraveling of Ms. Benge’s mystery disease began the week of May 11, 2009, when Ms. Benge, who is 56, and her sister Paula Allen, who is 51, arrived at the tall red-brick clinical center on the campus of the National Institutes of Health.

The Office of Undiagnosed Diseases had been hearing from thousands of patients, Dr. Gahl said, 1,700 of whom sent their medical records. “Many had been to Hopkins, the Mayo Clinic and the Cleveland Clinic, and some had been to all three and been there more than once,” he said.

Dr. Gahl and his colleagues were looking for people with unusual symptoms or unusual clues to what might be wrong. For example, they are now investigating a mystery disease in a young girl with uncontrollable muscle contractions that make it hard for her to talk, walk and use her hands; one that gave a young boy symptoms that look like Parkinson’s disease; and one that gives a middle-aged woman shards of keratin, a hair protein, coming out of her hair follicles.