Rapid, New Test Developed for Inherited Immune Deficiency
Newborn Screening Could Detect Bubble Boy Illness Early,
Save Lives
Contact: Geoff Spencer
301-402-0911
spencerg@mail.nih.gov
BETHESDA, Md., Tuesday, Feb. 22, 2005 - Researchers at
the National Human Genome Research Institute (NHGRI),
part of the National Institutes of Health (NIH), have
developed a new laboratory method that rapidly identifies
babies born with inherited forms of severe immune deficiency.
The new genetic test, which still must be validated before
widespread use, could someday be added to the panel of
tests that already screen newborns for a variety of disorders.
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| Wisconsin
is First State to Screen for `Bubble
Boy Disease'
MILWAUKEE _ On Jan. 1, 2008, Wisconsin
started screening all newborns for the
immune system disorder known as "bubble
boy disease."
The state is the first in the nation
to screen for severe combined immune
deficiency. The screen will be added
to the state's panel of newborn screens,
which includes a hearing test.
"This, once again, really establishes
the state of Wisconsin as being such
a progressive state," said John
Routes, professor of pediatrics at the
Medical College of Wisconsin.
The state now tests for 48 disorders,
well above the federal government's
recommendation of 29.
SCID is considered rare. One study
showed that fewer than one in every
100,000 newborns has the disease. But
because there have been no screening
programs to evaluate the true incidence,
experts suspect many more children might
have it _ and might be dying of SCID
infections before being diagnosed.
Routes said some cases of sudden infant
death syndrome might be the result of
this immune disorder.
"There is no hard data on what
the true incidence is in the state of
Wisconsin or anywhere," said Routes,
who is also medical director of allergy
and clinical immunology at Children's
Hospital of Wisconsin. "But I feel
pretty confident it will be higher than
one in 100,000."
The state's new screening program will
provide health officials the first glimpse
of the actual incidence.
It might also save many lives.
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The test identifies babies born with Severe Combined Immunodeficiency,
or SCID, an illness in which the infant fails to develop
a normal immune system. SCID babies can be infected by a
wide range of viruses, bacteria and fungi that are normally
controlled by a healthy baby's immune system. If undetected
and untreated, SCID typically leads to death before the
baby's first birthday. Developed in the NHGRI Division of
Intramural Research (DIR), the new test can use the same
dried blood samples already collected from newborns and
would provide the first accurate, high-throughput screen
for immune deficiencies. Prior efforts to identify this
disorder by counting white blood cells in newborns proved
unreliable and expensive.
"This new laboratory technique is an excellent example
of how increasingly sophisticated genetic tools can be
applied to important public health problems," said
NHGRI Scientific Director Eric D. Green, M.D., Ph.D. "Here
we have a chance to catch an illness early when treatment
is most effective. This new approach provides a rapid,
accurate indication of a possible immune problem immediately
after birth while the infant is protected by the mother's
antibodies still circulating in the baby's blood."
If SCID is diagnosed in time, there are effective treatments.
One form of the disease can be treated with an injectable
medication. All forms of the disorder can be cured through
the transplantation of bone marrow if a matching donor
can be identified. And finally, SCID may be treated through
human gene therapy in which a normal copy of the defective
gene may be inserted into the patient's own blood-forming
cells. The first gene therapy experiments in history were
carried out at NIH in 1990 in two young Ohio girls with
SCID. The patients are alive, continue to do well and
are involved in ongoing research at NHGRI.
The sooner a child is diagnosed, the sooner treatment
can begin and the more likely it is to be effective.
"Too many babies are diagnosed too late," said
Jennifer M. Puck, M.D., chief of NHGRI's Genetics and
Molecular Biology Branch. "And some babies develop
fatal infections before their condition is recognized.
Recent research shows that bone marrow transplants in
the first three months of life work better than transplants
at a later age. So it is critical to identify affected
children immediately after birth. Since the babies lack
overt clinical symptoms for some time, a molecular test
is a good approach."
The newly developed screening tool exploits a detailed
understanding of the maturation of T cells, one of the
essential types of white blood cells that make up the
immune system. Without a sufficient number of normal T
cells, the immune system doesn't work, just as when the
AIDS virus wipes out the same population of immune cells.
During normal development, an individual T cell rearranges
the gene that produces a so-called antigen receptor on
the surface of the cell. The antigen receptor allows the
T cell to identify an infectious agent and launch a defensive
attack to kill the invader.
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| Newborn Screening
The new spot test is still an experimental
method for screening for SCID and is not yet
available. Typical screening involves
a blood sample and a lymphocyte study.
Newborn Testing Could
Save Lives, DukeMedNews, April 2004. |
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While rearranging the receptor gene, the maturing T cell
produces a bit of leftover genetic material that forms a
ring structure within the cell. Using a quantitative laboratory
technique that measures the number of these rings within
a blood sample, Dr. Puck's group was able to differentiate
normal infants from those with SCID. In dried blood samples
from healthy babies, the team was able to detect an average
of 1,000 of these genetic rings; children with SCID had
30 or fewer. "That's a big difference," she said.
The development of the new test is described in the February
issue of The Journal of Allergy and Clinical Immunology.
Although the availability of the test raises the question
of whether states should begin using it on all newborns,
Dr. Puck concluded that the new test is not quite ready
for widespread use. It must first be validated.
"Our false positive rate was about 1.5 percent,
which is too high to be practical for screening,"
Dr. Puck said. A baby with a positive test would need
to be evaluated to see if he or she was actually sick;
a false positive rate of 1.5 percent would mean three
out of every 200 newborns would need further testing.
"That would be a lot of babies going back to the
doctor and a lot of worried parents. We are now working
on ways to decrease the number of false positives."
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| Two New UCLA
Studies Show Benefits of Newborn Screening
for ‘Bubble Boy Disease’
Two new UCLA studies show that newborn
screening for Severe Combined Immunodeficiency
(SCID) — a rare, treatable disorder
of the immune system commonly known as "bubble
boy disease" - is both cost-effective
and could be done accurately using a two-tiered
testing method. read
more |
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To validate the test, Dr. Puck's group is collaborating
with the newborn screening laboratory of the Maryland Department
of Health and Mental Hygiene in Baltimore. The Maryland
state lab is supplying some 5,000 blood samples already
collected on newborns for the NHGRI lab to test. Although
these samples are likely to be normal, they will be used
to refine the laboratory procedures and establish quality
control. Once the high-throughput screening approach has
been validated with this large set of existing samples from
Maryland, the NHGRI lab plans to begin prospectively testing
newborns from the state. Other state testing laboratories
also have expressed interest in participating in the prospective
studies.
Although considered a rare disease, SCID is best known
to the public from media accounts - and a made-for-TV
movie starring John Travolta - about David, the Bubble
Boy, a Texas boy who spent his entire life in a germ-free
environment, ultimately dying after a failed bone marrow
transplant in early adolescence. No one knows exactly
how many babies are born with SCID. Current estimates
suggest that 1 in every 50,000 to 100,000 births may be
affected, indicating SCID may be about as common as some
of the inherited illnesses for which states currently
screen all newborns. Experts suspect that many children
with SCID die from infections before being diagnosed,
so the true incidence of the disease may be even higher.
Newborn screening may reveal the true incidence.
Because the new test is still experimental, it is not
available to the general public and the cost has yet to
be determined.
NHGRI is one of the 27 institutes and centers at the
National Institutes of Health, which is an agency of the
Department of Health and Human Services. The NHGRI Division
of Intramural Research develops and implements technology
to understand, diagnose and treat genomic and genetic
diseases. Additional information about NHGRI can be found
at www.genome.gov
Original article can be found at http://genome.gov/13014329
Additional Links:
Two
New UCLA Studies Show Benefits of Newborn Screening for
‘Bubble Boy Disease’
Advisory
Committee on Heritable Disorders and Genetic Diseases
in Newborns and Children
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