NIH Clinical Center Profile 2012 - Search - National Institutes of Health

said Paula Allen, one of the ACDC patients in
the UDP. She and her sister, Louise Benge,
The UDP program, launched in May 2008, is
an initiative jointly led by the National Human
Genome Research Institute, the CC, and the NIH
Office of Rare Diseases Research. The program
receives referrals from around the country when
cases challenge the medical community at large.
Patients visit the CC for extensive medical diagnostic
testing and evaluation.
“When we first announced the Undiagnosed Diseases
Program, we had two goals: to provide hope
for patients whose diseases had eluded diagnosis
and to conduct fundamental medical research on
the causes of diseases,” said Dr. William Gahl, UDP
director. “From the start, we expected that this
pursuit might lead to the discovery of new diseases
and of variations of known diseases.”
Researchers saw members of two families with
ACDC, and identified a third case outside the
country. Seven medical cases like those described
in this study have been reported in medical
journals over the past century, but these previous
studies did not include any insights about the
molecular basis of the disorder.
The patients seen at the CC experienced pain and
cramping in the calves, thighs, buttocks, and feet
due to poor circulation. MRIs and X-rays showed
calcium deposits in artery walls.
In the case of Allen and Benge, two of five affected
siblings, clinical researchers suspected a recessive
inheritance, in which offspring receive two copies
of a gene variant — one from each parent — that
produces disease symptoms only when combined.
The researchers analyzed DNA from all members
of the family and found regions where the siblings’
DNA contained two copies of a particular DNA
segment compared to their parents’ DNA, which
contained just a single copy.
The comparison revealed one such region, which
the researchers then analyzed for variants not present
in a population of 200 unaffected people. The
siblings all had the same variant in a gene called
NT5E. This gene normally makes the extracellular
protein CD73, which produces a small molecule,
adenosine, which protects the arteries from calcifying.
The researchers also detected variants in NT5E
in all the other affected patients in the study.
Study evaluates reported versus
actual food intake
A recent study conducted at the Clinical Center
and published in the journal Eating Behaviors by
a team from the NIH and the Uniformed Services
University of Health Sciences cited marked
differences in reported versus actual food intake
in youth with an eating behavior called loss-ofcontrol
eating.
“Loss-of-control eating is when someone feels like
they don’t have control over what or how much
they are eating. Some describe it as ‘numbing out’
for a while and just eating without feeling a lot of
control,” said Merel Kozlosky, supervisory metabolic
dietitian and director of the CC Nutrition
Department’s dietetic internship program, who
served as the dietitian on this research study.
Although it is difficult to measure, loss-of-control
eating affects between two and 10 percent of children
and adolescents, and is associated with higher
body fat, higher likelihood of being overweight,
and more weight gained. “We know that a lot of
2 5 • A N N U A L R E P O RT 2 0 1 2
A knee X-ray of a CC
patient with ACDC
reveals calcification
in the main artery
supplying blood to
the lower leg. Such an
abnormal occurrence
causes pain and
restricts mobility.