The genetic basis for a previously unexplained medical condition which
causes a painful hardening of the arteries has been identified by the US
Undiagnosed Diseases Program (UDP).
Known simply as 'artery-calcification', the rare condition involves a calcium
build-up in arteries below the waist and in the joints of patient's hands and
feet. It has been observed in only nine individuals from three unrelated
Researchers analysed the DNA of nine individuals affected by the disorder and
identified a mutation in the NT5E gene. The gene is for enzyme CD73 known to convert
adenosine monophosphate (AMP) to adenosine, a molecule believed to inhibit the
calcification process. A loss of CD73 can lead to a build-up of AMP resulting
in a hardening of the arteries.
Despite the disorder sharing common symptoms with rheumatoid arthritis, the researchers
stress that it is a wholly new disorder.
The findings could offer an avenue for treatment although the significance of
the findings may not be known for a number of years, said UDP director Dr William
Gahl. Experiments normalised CD73 and alkaline phosphate activity in the patients'
cells. Alongside this, adenosine treatment also reduced the alkaline phosphate
concentration and calcification.
'The role of adenosine was not known before', explained Dr Gahl.
Researchers hope the results could help advance treatments of more common
diseases with similar symptoms, for example atherosclerosis, in which arteries
hardened and become clogged.
The US National Institute of Health (NIH) established the UDP in 2008 as
part of an initiative jointly led by the National Human Genome Research
Institute (NHGRI), the NIH Clinical Centre and the NIH Office of Rare Diseases
The findings were published in the New England Journal of Medicine.