Got a question
about
Ataxia-Telangiectasia?
About
Primary Immune Deficiency
IDF PATIENT/FAMILY HANDBOOK | CHAPTER XI
Ataxia-Telangiectasia
Ataxia Telangiectasia (A-T) is a primary immunodeficiency disease
which affects a number of different organs in the body. It is
characterized by: neurologic abnormalities resulting in an unsteady
gait (ataxia), dilated blood vessels (telangiectasia) of the eyes and
skin, a variable immunodeficiency involving both cellular
(T-lymphocyte) and humoral (B-lymphocytes) immune responses
and a predisposition to cancer.
 Definition of Ataxia Telangiectasia:
Ataxia Telangiectasia (A-T) is a primary
immunodeficiency disease which affects a number
of different organs in the body. It is characterized
by: neurologic abnormalities resulting in an
unsteady gait (ataxia), dilated blood vessels
(telangiectasia) of the eyes and skin, a variable
immunodeficiency involving both cellular
(T-lymphocyte) and humoral (B-lymphocytes)
immune responses and a predisposition to cancer.
Back to top
Clinical Presentation of Ataxia Telangiectasia:
The first presenting symptom is generally ataxia,
a medical term used to describe an unsteady
gait. Children with Ataxia Telangiectasia (A-T) may
sway when they stand or sit and they wobble or
stagger when they walk. Ataxia usually results
from neurologic abnormalities affecting a part of
the brain (the cerebellum) that controls balance.
A-T first becomes apparent when the child begins
to walk, typically between 12 and 18 months of
age. At this early point in time, many children are
thought to have cerebral palsy or an undefined
neurologic disorder. The specific diagnosis of A-T
may be difficult to make when symptoms first
appear. Later, neurological symptoms include
abnormalities in eye movements, including rapidly
alternating twitches of the eyes (nystagmus) and
difficulty in initiating voluntary eye movements
(oculomotor apraxia). Patients with A-T also
develop difficulty using the muscles needed for
speech (dysarthria) and swallowing. Often, the
diagnosis of A-T is only suspected when the
neurologic problems start to become progressively
worse, typically at age 5-6 years.
Dilated blood vessels (telangiectasia) become
apparent after the onset of the ataxia, generally
between 2 and 8 years of age. Telangiectasia
usually occurs on the white portion of the eye
(bulbar conjunctiva) but may also be found on the
ears, neck and extremities. However, telangiectasia
does not develop in all people with A-T.
Another clinical feature of A-T is an increased
susceptibility to infections. This symptom is a
major feature in some individuals. Infections most
commonly involve the lungs and sinuses and
are usually caused by bacteria or viruses. The
infections are, at least in part, due to the variable
immunodeficiency seen in A-T. Another factor that
may contribute to lung infections is the swallowing
dysfunction that results in aspiration with solid
food and liquid going down the passageway to the
lungs (the trachea) instead of the passageway to
the stomach (the esophagus).
Patients with A-T may have defects in both their
T-lymphocyte system and B-lymphocyte system.
They may have reduced numbers of T-lymphocytes
in their blood. These abnormalities in T-lymphocytes
are usually associated with a small or immature
thymus gland. The low number of T-lymphocytes
generally does not increase the patient's
susceptibility to infection. Most patients with A-T
produce some antibody responses against foreign
antigens, such as microorganisms, but some of
these responses may be impaired, particularly
those responses directed against the large sugar
molecules (polysaccharides) found on the outside
of bacteria that cause respiratory infections. These
disordered antibody responses may be associated
with low levels of immunoglobulins–especially
deficiencies of IgA, IgE and IgG subclasses
(see chapter titled IgG Subclass Deficiency and
Specific Antibody Deficiency). Finally, patients with
A-T have an increased risk for developing cancer,
particularly cancers of the immune system, such
as lymphoma and leukemia.
Back to top
Diagnosis of Ataxia Telangiectasia:
The diagnosis of Ataxia Telangiectasia (A-T) is
usually based on characteristic clinical findings
and supported by laboratory tests. Once all of
the clinical signs and symptoms of A-T have
become obvious in an older child or young adult,
the diagnosis is relatively easy. The most difficult
time to diagnose A-T is during the period when
neurologic symptoms are first apparent (early
childhood) and the typical telangiectasia has
not yet appeared. During this period, a history
of recurrent infections and typical immunologic
findings can be suggestive of the diagnosis. One
of the most helpful laboratory tests used to assist
in the diagnosis of A-T is the measurement of
alpha-fetoprotein levels in the blood. This is a
protein that is usually produced only 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 (>95%) have elevated
levels of serum alpha-fetoprotein. When other
causes of elevations of alpha-fetoprotein are
eliminated, elevated alpha-fetoprotein in the blood,
in association with the characteristic signs and
symptoms, makes the diagnosis of A-T a virtual
certainty.
Other diagnostic tests include:
- Detection of the protein (ATM) made by the A-T
gene using a western blot
- Measurement of cellular damage (cell death or
chromosomal breakage) after exposure of cells
to x-rays in the laboratory
- Sequencing (reading the spelling) of the A-T
gene (ATM)
Back to top
Inheritance of Ataxia Telangiectasia: Ataxia Telangiectasia is inherited as an autosomal
recessive disorder (see chapter titled Inheritance).
The gene responsible for A-T has been identified
and is found on the long arm of chromosome
11 at 11q22-23. It controls the production of
a phosphatidylinositol-3-kinase-like enzyme
involved in cellular responses to stress, DNA
damage and cell cycle control. The identification
of the specific gene responsible for A-T has made
carrier detection and prenatal diagnosis possible,
though it can be done only in a few specialized
laboratories and is very expensive.
Back to top
General Treatment for Ataxia Telangiectasia:
There is no cure for any of the problems in
Ataxia Telangiectasia (A-T), and treatment is
largely supportive. Patients of all ages should be
encouraged to participate in as many activities
as possible. Children should be able to attend
school on a regular basis, but most will eventually
need full-time classroom aides. Progressive eye
movement abnormalities make reading difficult,
but listening skills do not deteriorate. As a result,
it is helpful to introduce books-on-tape at a young
age to foster development of listening skills.
Computers are also helpful learning aides that
can be easily adapted to the specific needs of an
individual who has problems with eye and hand
coordination. Physical and occupational therapists
should be included in the treatment team to
prevent the development of stiffness in muscles
and to maintain functional mobility.
A prompt diagnosis should be sought for all
suspected infections and specific therapy
instituted. For patients who have normal levels
of serum immunoglobulins and normal antibody
responses to vaccines, immunization with
influenza (flu) and pneumococcal vaccines may be
helpful. For patients with total IgG, or IgG subclass
deficiencies, and/or patients who have problems
making normal antibody responses to vaccines,
immunoglobulin replacement therapy may be
indicated. In an effort to decrease exposure to the
flu, all household members should receive the flu
vaccine every fall.
Special attention should be paid to the lungs.
A-T patients have difficulty taking deep breaths
and coughing to clear mucus from the airways.
They may benefit from daily chest physiotherapy
or use of a therapy vest. If chronic lung disease
develops, a lung specialist should be consulted
about the use of intermittent antibiotic prophylaxis,
inhaled medicines to decrease airway inflammation
or constriction and the need for supplemental
oxygen while sleeping. Many A-T patients develop
problems with chewing and swallowing. Those
who aspirate (have food and liquids entering their
windpipe and lungs) may improve when thin liquids
are eliminated from their diet. In some individuals,
a tube from the stomach to the outside of the
abdomen (gastrostomy tube) may be necessary to
eliminate the need for swallowing large volumes of
liquids and to decrease the risk of aspiration.
Diagnostic X-rays should be limited because of
the theoretical risk that the X-rays may cause
chromosomal damage. In general, X-rays should
only be done if the result will influence therapy and
there is no other way to obtain the information that
the X-ray will provide.
Back to top
Specific Therapy for Ataxia Telangiectasia:
Specific therapy for the neurologic problems
of A-T is not possible at the present time. The
use of thymic transplants, thymic hormones
and bone marrow transplantation has not led to
improvement. Similarly, there is no evidence that
any specific supplemental nutritional therapy is
beneficial. However, now that the gene has been
identified and the gene's normal function is being
studied, hopefully new and specific therapy may
become available.
Back to top
Expectations for the Ataxia Telangiectasia Patient:
In general, Ataxia Telangiectasia (A-T) follows a
progressive course. It must be stressed that the
course of the disease can be quite variable and
it is difficult to predict the course in any given
individual. Even within families, where the specific
genetic defect is the same, there can be great
variability in the type and severity of different
neurologic problems and immunodeficiency.
The course of the disease in most patients
is characterized by progressive neurologic
deterioration. Many patients are confined to a
wheelchair in their teens. Infections of the lungs
(bronchitis or pneumonia) and sinuses (sinusitis)are common and may damage the lungs even
if treated promptly. Malignancies or cancers are
also more common in patients with A-T. They can
be treated but require modifications of standard
chemotherapy protocols. For example, A-T patients
should never receive radiation therapy for cancer.
It should be emphasized, that although the above
course is the most typical, the course of A-T
varies considerably from patient to patient. Some
patients have been able to attend college and live
independently, and some have lived into the fifth
decade of life.
Back to top
|
