Old Pain Has a New Name

An x-ray image of the knee of a patient with a disorder called arterial calcification due to CD73 deficiency, or ACDC, reveals calcification in the main artery supplying blood to the lower leg. Scientists have now identified a gene mutation that causes ACDC.

A rare vascular disorder that baffled clinicians for a century now has a name: arterial calcification due to CD73 deficiency, or ACDC. Researchers from the National Institutes of Health (NIH) Undiagnosed Disease Program who identified the genetic cause of the painful disease explain their findings in today’s New England Journal of Medicine.

“This is a major advance in biology,” William Gahl, MD, PhD, director of the NIH’s 3-year-old Undiagnosed Disease Program, said during a press briefing.

The hunt for the disorder’s underpinnings began 2 years ago when a Mount Vernon, Ky, physician referred 2 sisters to the NIH. Both had severe pain in their hands and legs. Imaging tests had shown that they had calcium deposits that blocked blood flow in the arteries of their hips, legs, and hands. Their debilitating pain defied diagnosis for 3 decades.

After studying all 5 members of the Kentucky family and 2 unrelated families, researchers identified 9 individuals with ACDC. Genetic analyses of DNA from unaffected parents, their children who have the disorder, and 200 individuals serving as controls found that a mutation in the NT5E gene causes the disorder.

The NT5E gene encodes CD73 protein, which produces the adenosine molecule that protects arteries from calcifying. But individuals who have 2 copies of the mutation do not have enough CD73 protein to produce sufficient adenosine to prevent calcium build-up in some arteries. ACDC does not affect the coronary arteries.

No treatment currently exists for ACDC. But Manfred Boehm, MD, an investigator at the National Heart, Lung, and Blood Institute, said during the briefing that bisphosphonates, which are used to treat a severe calcification disorder in infants as well as osteoporosis, might be effective against ACDC.

“There are experimental drugs to modulate adenosine,” he added. “We will continue in vitro studies to find the best drug.”

Categories: Cardiovascular System, Genetic Disorders, Pain