Ataxia telangiectasia (A-T), also called Louis-Bar syndrome or
cerebello-oculocutaneous telangiectasia, is a rare, inherited disease that
attacks the neurological and immune systems of children. A-T is a
recessive disorder, meaning that it affects children who carry two copies
of a defective (mutated) A-T gene, one copy from each parent. A-T affects
the brain and many parts of the body and causes a wide range of severe
Ataxia means poor coordination, and the telangiectasia are tiny, red
spider blood vessels which develop in A-T patients, especially on the
whites of the eyes and on the surface of the ears. A-T is a progressive
disease that affects the cerebellum (the body's motor control
center) and, in about 70 percent of cases, weakens the immune system as
well, leading to respiratory disorders. The weakening of the immune system
) resulting from A-T has been traced to defects in both B-cells and
T-cells, the specialized white blood cells (lymphocytes) that defend the
body against infection, disease, and foreign substances. In A-T children,
B-cell responses are very weak, and levels of immunoglobulins, the
proteins that B-cells make to fight infection by specific recognition of
invading organisms, may also be low. T-cells are few and weak, and the
thymus gland is immature. This is why A-T is also considered an
immunodeficiency disease. A-T first shows itself in early childhood,
usually at the toddler stage. The characteristic symptoms are lack of
balance, slurred speech, and perhaps a higher-than-normal number of
infections. All children at this age take a little while to develop good
walking skills, coherent speech, and an effective immune system, so it
often takes a few years before A-T is correctly diagnosed. Other features
of the disease may include mild diabetes, premature graying of the hair,
difficulty swallowing, and delayed physical and sexual development.
Children with A-T usually have normal or above normal
, but some cases of
have been reported.
A-T is genetically transmitted by parents who are carriers of the gene
responsible for A-T. The A-T mode of inheritance is autosomal recessive
(AR) and requires two copies of the predisposing gene—one from each
parent—for the child to have the disease. Parents do not exhibit
symptoms, but they each carry a recessive gene that may cause A-T in their
offspring. In AR families, there is one chance in four that each child
born to the parents will have the disorder. Every healthy sibling of an
A-T patient has a 66 percent chance of being a carrier, like the parents.
According to the National
Institute, the incidence of A-T is between one out of 40,000 and one out
of 100,000 persons worldwide, and for Caucasians it is about three per
million, so the disorder is very rare. In the United States, there are
about 500 children with A-T with both males and females equally affected.
An estimated 1 percent (2.5 million) of the general population carries one
of the defective A-T genes. Carriers of one copy of this gene do not
develop A-T but have a significantly increased risk of cancer (over 38
percent of children with A-T develop cancer).
Causes and symptoms
A-T is a genetic disorder, meaning that it is caused by a defect in a gene
that is present in a person at birth. All people have genes that contain a
few mistakes or variations that do not result in a disorder. Disorders
result when the gene variations are significant enough to affect the
function a gene controls. Variations that cause disease are called
mutations and A-T results from a defective gene, the ATM gene (for ataxia
telangiectasia, mutated), first identified in 1995. The ATM gene is
located on the long arm of chromosome 11 at position 11q22-23. It encodes
for (controls) the production of a protein that plays a role in regulating
cell division following DNA damage. The various symptoms seen in A-T
reflect the main role of this protein, which is to induce several cellular
responses to DNA damage. The protein made by the ATM gene is located in
the nucleus of the cell and normally functions to control the rate at
which the cell grows. The ATM protein does this by sending
signals and modifying other proteins in the cell, which then changes the
function of the proteins. The ATM protein also interacts with other
special proteins when DNA is damaged as a result of exposure to some type
of radiation. If the strands of DNA are broken, the ATM protein
coordinates DNA repair by activating repair proteins, which helps to
maintain the stability of cells. Mutations in ATM prevent cells from
repairing DNA damage, which may lead to cancer. Mutations can also signal
cells in the brain to die inappropriately, causing the movement and
coordination problems associated with A-T.
A-T affects several different organs in the body. The most important
symptoms are as follows:
Additional clinical symptoms include the following:
A-T children appear normal as infants. The decreased coordination of
movements (ataxia) associated with A-T first becomes apparent when a child
begins to walk, typically between 12 and 18 months of age. Toddlers with
A-T are usually wobbly walkers. In their
years, children with A-T begin to stumble and fall, and drooling is
frequent. Parents should contact their pediatrician if they observe any
A-T signs or symptoms in their child. Telangiectasias are another typical
warning sign. They become apparent after the onset of the ataxia, often
between two and eight years of age.
Establishing a diagnosis for ataxia telangiectasia is most difficult in
very young children, primarily because the full-blown syndrome is not yet
apparent. As of 2004, the A-T diagnosis is usually based on the
characteristic clinical findings and supported by laboratory tests that
point to a defect of DNA (genes and chromosomes) and to an inability to
repair some types of damage to DNA. Laboratory tests are helpful but not
as important as the individual patient's symptoms and signs,
history, and complete neurological evaluation including a
magnetic resonance imaging
(MRI) scan of the brain. The cerebellum atrophies early in the disease,
being visibly smaller on MRI examination by seven or eight years of age.
Diagnosis is more difficult before the disorder has fully developed, when
the child is still uncertain on his/her feet. The most difficult time to
diagnose A-T is during the period when neurologic symptoms start to appear
(early childhood) and the typical telangiectasias have not yet appeared.
During this period, a history of recurrent infections and typical
immunologic findings can suggest the diagnosis. Four tests are used to
help establish the A-T diagnosis:
The ionizing irradiation sensitivity test is the most useful test for
diagnosing A-T. However, it can only be carried out in specialized centers
and takes much longer than the other tests.
Because of its variable symptoms, A-T is often misdiagnosed as a form of
or as slow development.
As of 2004, there is no cure for ataxia telangiectasia, thus specific
therapy is not available, and treatment is largely supportive. Patients
are encouraged to participate in as many activities as possible. Children
are encouraged to attend school on a regular basis and receive support to
maintain as normal a lifestyle as possible. The following are some types
of interventions have been shown to help those with the disorder:
Because cells from patients with A-T are 30 percent more sensitive to
ionizing radiation than the cells of normal individuals, any required
should be reduced or monitored carefully; conventional doses are
contraindicated and are potentially lethal.
—An inherited condition that causes a lack of pigment. People
with albinism typically have light skin, white or pale yellow hair, and
light blue or gray eyes.
—One of two or more alternate forms of a gene.
—A condition marked by impaired muscular coordination, most
frequently resulting from disorders in the brain or spinal cord.
—The progressive wasting and loss of function of any part of the
B-cell (B lymphocyte)
—A small white blood cell from bone marrow responsible for
producing antibody and serving as a precursor for plasma cells.
—A person who possesses a gene for an abnormal trait without
showing signs of the disorder. The person may pass the abnormal gene on
to offspring. Also refers to a person who has a particular disease agent
present within his/her body, and can pass this agent on to others, but
who displays no symptoms of infection.
Central nervous system
—Part of the nervous system consisting of the brain, cranial
nerves, and spinal cord. The brain is the center of higher processes,
such as thought and emotion and is responsible for the coordination and
control of bodily activities and the interpretation of information from
the senses. The cranial nerves and spinal cord link the brain to the
peripheral nervous system, that is the nerves present in the rest of
—The part of the brain involved in the coordination of movement,
walking, and balance.
—A microscopic thread-like structure found within each cell of
the human body and consisting of a complex of proteins and DNA. Humans
have 46 chromosomes arranged into 23 pairs. Chromosomes contain the
genetic information necessary to direct the development and functioning
of all cells and systems in the body. They pass on hereditary traits
from parents to child (like eye color) and determine whether the child
will be male or female.
—A disease characterized by an inability to process sugars in the
diet, due to a decrease in or total absence of insulin production.
—Deoxyribonucleic acid; the genetic material in cells that holds
the inherited instructions for growth, development, and cellular
—Proteins that are usually produced during fetal development but
may persist at high blood levels in some conditions (such as A-T) after
birth. The vast majority of A-T patients (more than 95%) have elevated
levels of serum alpha-fetoprotein.
—A building block of inheritance, which contains the instructions
for the production of a particular protein, and is made up of a
molecular sequence found on a section of DNA. Each gene is found on a
precise location on a chromosome.
—A physiological response of the body controlled by the immune
system that involves the production of antibodies to fight off specific
foreign substances or agents (antigens).
—The system of specialized organs, lymph nodes, and blood cells
throughout the body that work together to defend the body against
foreign invaders (bacteria, viruses, fungi, etc.).
—A condition in which the body's immune response is
damaged, weakened, or is not functioning properly.
Immunoglobulin G (IgG)
—Immunoglobulin type gamma, the most common type found in the
blood and tissue fluids.
—A cancer of the blood-forming organs (bone marrow and lymph
system) characterized by an abnormal increase in the number of white
blood cells in the tissues. There are many types of leukemias and they
are classified according to the type of white blood cell involved.
—A type of white blood cell that participates in the immune
response. The two main groups are the B cells that have antibody
molecules on their surface and T cells that destroy antigens.
—An acute form of childhood leukemia characterized by the
development of abnormal cells in the bone marrow.
—A diverse group of cancers of the lymphatic system characterized
by abnormal growth of lymphatic cells. Two general types are commonly
recognized–Hodgkin's disease and non-Hodgkin's
Magnetic resonance imaging (MRI)
—An imaging technique that uses a large circular magnet and radio
waves to generate signals from atoms in the body. These signals are used
to construct detailed images of internal body structures and organs,
including the brain.
—Controlled movements of muscle groups. Fine motor skills involve
tasks that require dexterity of small muscles, such as buttoning a
shirt. Tasks such as walking or throwing a ball involve the use of gross
—A disease in which the nervous system progressively and
—An involuntary, rhythmic movement of the eyes.
—Advancing, going forward, going from bad to worse, increasing in
scope or severity.
—Disorder that requires two copies of the predisposing gene one
from each parent for the child to have the disease.
—An undifferentiated cell that retains the ability to develop
into any one of a variety of cell types.
—A type of white blood cell that is produced in the bone marrow
and matured in the thymus gland. It helps to regulate the immune
system's response to infections or malignancy.
—Abnormal dilation of capillary blood vessels leading to the
formation of telangiectases or angiomas.
—A lack of T lymphocytes, due to failure of the thymus to
develop, resulting in very reduced immunity.
Parents may consider enrolling their A-T diagnosed child in a NIH-approved
clinical trial. The first-ever A-T clinical treatment study took place at
Children's Hospital in Philadelphia, with a second trial that
started in 2000. In 2004, the A-T Clinical Center at Johns Hopkins
Hospital in Baltimore also started a clinical study. Children who
participate in these clinical trials receive complete immunological and
neurological evaluations as part of being enrolled in the study. Many
patients also receive nutritional evaluations and consultations as well.
Some A-T patients have impaired swallowing function. Patients who aspirate
or have food and liquids reaching their lungs have been shown to improve
when thin liquids are removed from their diet. In some individuals, a tube
from the stomach to the outside of the abdomen (gastrostomy tube) may be
required to eliminate the need for swallowing large volumes of liquids and
to decrease the risk of aspiration. Vitamin E supplements are often
recommended, although the vitamin has not been formally tested for
efficacy in patients with A-T.
Generally, the prognosis for individuals with A-T is poor. Those with the
disease are frequently wheelchair-bound by their teens and usually die in
their teens or early 20s. However, the course of the disease can be quite
variable, and it is difficult to predict the outcome for any given
individual as A-T varies considerably from patient to patient. Even within
families, in which the specific genetic defect should be the same, some
children have mostly neurologic problems while others have recurrent
infections, and still others have neither neurologic problems nor
There was no cure for A-T as of 2004. The cloning and sequencing of the
ATM gene has opened several avenues of research with the goal of
developing better treatment, including gene therapy and the design of
drugs for more effective treatments. Research is also leading to a greater
understanding of AT, increased awareness, and more genetic counseling.
In the past, A-T carriers were identified because they were parents of a
child diagnosed with A-T. But the cloning of the ATM gene responsible for
A-T as of 2004 allows physicians or cancer genetics professionals to
conduct genetic testing, analyzing patients' DNA to look for A-T
mutations in the ATM gene. Thus, prenatal diagnosis can be carried out in
most families. Genetic counseling is also of benefit to prospective
parents with a family history of ataxia-telangiectasia. Parents of a child
diagnosed with A-T may have a slight increased risk of cancer. They
should have genetic counseling and more intensive screening for cancer.
Any family touched by ataxia telangiectasia is forever affected. Old
assumptions have to be discarded and new, often very difficult, realities
need to be accepted, including the uncertainty of the A-T outcome.
Significant adjustments, both physical and psychological, are required,
many of them agonizingly difficult. A-T support groups have been organized
by all major A-T organizations, such as the Ataxia Telangiectasia
Children's Project, the National Ataxia Foundation (NAF), and the
Ataxia Telangiectasia Medical Research Foundation. These organizations are
dedicated to improving the lives of families affected by A-T. They also
provide the latest news on A-T research, information on coping with A-T,
and personal accounts of living with A-T.
Magnetic resonance imaging
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Ataxia Telangiectasia (A-T) Children's Project.
668 South Military Trail, Deerfield Beach, FL 33442–3023. Web
Ataxia Telangiectasia (A-T) Medical Research Foundation.
5241 Round Meadow Road, Hidden Hills, CA 91302. Web site:
National Ataxia Foundation (NAF).
2600 Fernbrook Lane, Suite 119, Minneapolis, MN 55447–4752. (763)
Web site: http://www.ataxia.org.
National Institute of Child Health and Human Development (NICHD).
31 Center Drive, Rm. 2A32, MSC 2425, Bethesda, MD 20892–2425. Web
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PO Box 1968, 55 Kenosia Avenue, Danbury, CT 06813–1968. (203)
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