What is Friedreich's ataxia?
Friedreich's ataxia (also called FA
or FRDA) is a rare inherited disease that causes nervous system damage
and movement problems.
It usually begins in childhood and
leads to impaired muscle coordination (ataxia) that worsens over time.
The disorder is
named after Nicholaus Friedreich, a
German doctor who first described the condition in the 1860s.
In Friedreich’s ataxia the spinal
cord and peripheral nerves degenerate, becoming thinner. The cerebellum,
part of the brain
that coordinates balance and
movement, also degenerates to a lesser extent. This damage results in
awkward, unsteady movements
and impaired sensory functions. The
disorder also causes problems in the heart and spine, and some people
with the condition
develop diabetes. The disorder does
not affect thinking and reasoning abilities (cognitive functions).
Friedreich’s
ataxia is caused by a defect (mutation) in a gene labeled FXN. The
disorder is recessive, meaning it occurs only
in someone who inherits two
defective copies of the gene, one from each parent. Although rare,
Friedreich’s ataxia is the
most common form of hereditary
ataxia, affecting about 1 in every 50,000 people in the United States.
Both male and female
children can inherit the disorder.
What are the signs and symptoms?
Symptoms typically begin between the
ages of 5 and 15 years, although they sometimes appear in adulthood and
on rare occasions
as late as age 75. The first symptom
to appear is usually gait ataxia, or difficulty walking. The ataxia
gradually worsens
and slowly spreads to the arms and
the trunk. There is often loss of sensation in the extremities, which
may spread to other
parts of the body. Other features
include loss of tendon reflexes, especially in the knees and ankles.
Most people with Friedreich's
ataxia develop scoliosis (a curving
of the spine to one side), which often requires surgical intervention
for treatment.
Dysarthria (slowness and slurring of speech) develops and can get progressively worse. Many individuals with later stages
of Friedreich’s ataxia develop hearing and vision loss.
Other symptoms that may occur
include chest pain, shortness of breath, and heart palpitations. These
symptoms are the result
of various forms of heart disease
that often accompany Friedreich's ataxia, such as hypertrophic
cardiomyopathy (enlargement
of the heart), myocardial fibrosis
(formation of fiber-like material in the muscles of the heart), and
cardiac failure. Heart
rhythm abnormalities such as
tachycardia (fast heart rate) and heart block (impaired conduction of
cardiac impulses within
the heart) are also common.
About 20 percent of people with
Friedreich's ataxia develop carbohydrate intolerance and 10 percent
develop diabetes. Most
individuals with Friedreich’s ataxia
tire very easily and find that they require more rest and take a longer
time to recover
from common illnesses such as colds
and flu.
The rate of progression varies from
person to person. Generally, within 10 to 20 years after the appearance
of the first symptoms,
the person is confined to a
wheelchair, and in later stages of the disease individuals may become
completely incapacitated.
Friedreich's ataxia can shorten life
expectancy, and heart disease is the most common cause of death.
However, some people
with less severe features of
Friedreich's ataxia live into their sixties, seventies, or older.
How is Friedreich's ataxia diagnosed?
A diagnosis of Friedreich's ataxia
requires a careful clinical examination, which includes a medical
history and a thorough
physical exam, in particular looking
for balance difficulty, loss of proprioception (joint sensation),
absence of reflexes,
and signs of neurological problems.
Genetic testing now provides a conclusive diagnosis. Other tests that
may aid in the diagnosis
or management of the disorder
include:
- electromyogram (EMG), which measures the electrical activity of muscle cells,
- nerve conduction studies, which measure the speed with which nerves transmit impulses,
- electrocardiogram (ECG), which gives a graphic presentation of the electrical activity or beat pattern of the heart,
- echocardiogram, which records the position and motion of the heart muscle,
- blood tests to check for elevated glucose levels and vitamin E levels, and
- magnetic resonance imaging (MRI) or computed tomography (CT) scans, tests which provide brain and spinal cord images that
are useful for ruling out other neurological conditions.
How is Friedreich's ataxia inherited?
Friedreich's ataxia is an autosomal
recessive disease, meaning individuals only develop symptoms if they
inherit two copies
of the defective FXN gene, one from
their father and one from their mother. A person who has only one
abnormal copy of the
gene is called a carrier. A carrier
will not develop the disease but could pass the gene mutation on to his
or her children.
If both parents are carriers, their
children will have a 1 in 4 chance of having the disease and a 1 in 2
chance of inheriting
one abnormal gene that they, in
turn, could pass on to their children. About one in 90 Americans of
European ancestry carries
an abnormal FXN gene.
In 1996, an international research
team identified the Friedreich’s ataxia gene on chromosome 9. The FXN
gene codes for production
of a protein called "frataxin." In
the normal version of the gene, a sequence of DNA (labeled “GAA”) is
repeated between 7
and 22 times. In the defective FXN
gene, the repeat occurs over and over again—hundreds, even up to a
thousand times.
This abnormal pattern, called a triplet repeat
expansion, has been implicated as the cause of several dominantly
inherited
diseases, but Friedreich's ataxia is
the only known recessive genetic disorder caused by the problem. Almost
all people with
Friedreich's ataxia have two copies
of this mutant form of FXN, but it is not found in all cases of the
disease. About two
percent of affected individuals have
other defects in the FXN gene that are responsible for causing the
disease.
The triplet repeat expansion greatly
disrupts the normal production of frataxin. Frataxin is found in the
energy-producing
parts of the cell called
mitochondria. Research suggests that without a normal level of frataxin,
certain cells in the body
(especially peripheral nerve, spinal
cord, brain and heart muscle cells) cannot effectively produce energy
and have been hypothesized
to have a buildup of toxic
byproducts leading to what is called “oxidative stress.” It also may
lead to increased levels of
iron in the mitochondria. When the
excess iron reacts with oxygen, free radicals can be produced. Although
free radicals are
essential molecules in the body's
metabolism, they can also destroy cells and harm the body. Research
continues on this subject
(see section on “What research is
being done?”).
Can Friedreich's ataxia be cured or treated?
As with many degenerative diseases
of the nervous system, there is currently no cure or effective treatment
for Friedreich's
ataxia. However, many of the
symptoms and accompanying complications can be treated to help
individuals maintain optimal functioning
as long as possible. Doctors can
prescribe treatments for diabetes, if present; some of the heart
problems can be treated
with medication as well. Orthopedic
problems such as foot deformities and scoliosis can be corrected with
braces or surgery.
Physical therapy may prolong use of
the arms and legs. Advances in understanding the genetics of
Friedreich's ataxia are leading
to breakthroughs in treatment.
Research has moved forward to the point where clinical trials of
proposed treatments are presently
occurring for Friedreich’s ataxia.
What services are useful to Friedreich's ataxia patients and their families?
Genetic testing is essential for
proper clinical diagnosis, and can aid in prenatal diagnosis and
determining a person’s carrier
status. Genetic counselors can help
explain how Friedreich's ataxia is inherited. Psychological counseling
and support groups
for people with genetic diseases may
also help affected individuals and their families cope with the
disease.
A primary care physician can screen
people for complications such as heart disease, diabetes and scoliosis,
and can refer
individuals to specialists such as
cardiologists, physical therapists, and speech therapists to help deal
with some of the
other associated problems.
Support and information for families
is also available through a number of private organizations. These
groups can offer ways
to network and communicate with
others affected by Friedreich’s ataxia. They can also provide access to
patient registries,
clinical trials information, and
other useful resources.
What research is being done?
Within the Federal government the
National Institute of Neurological Disorders and Stroke (NINDS), a
component of the National
Institutes of Health (NIH), has
primary responsibility for sponsoring research on neurological
disorders. As part of this
mission, the NINDS conducts research
on Friedreich's ataxia and other forms of inherited ataxias at its
facilities at the
NIH and supports additional studies
at medical centers throughout the United States. Several nonprofit
organizations also
provide substantial support research
(see the section on "Where can I get more information?").
Researchers are optimistic that they
have begun to understand the causes of the disease, and work has begun
to develop effective
treatments and prevention strategies
for Friedreich's ataxia. Scientists have been able to create various
models of the disease
in yeast and mice which have
facilitated understanding the cause of the disease and are now being
used for drug discovery
and the development of novel
treatments.
Studies have revealed that frataxin
is an important mitochondrial protein for proper function of several
organs. Yet in people
with the disease, the amount of
frataxin in affected cells is severely reduced. It is believed that the
loss of frataxin makes
the nervous system, heart, and
pancreas particularly susceptible to damage from free radicals (produced
when the excess iron
reacts with oxygen). Once certain
cells in these tissues are destroyed by free radicals they cannot be
replaced. Nerve and
muscle cells also have metabolic
needs that may make them particularly vulnerable to this damage. Free
radicals have been
implicated in other degenerative
diseases such as Parkinson's and Alzheimer's diseases.
Based upon this information,
scientists and physicians have tried to reduce the levels of free
radicals, also called oxidants,
using treatment with “antioxidants.”
Initial clinical studies in Europe suggested that antioxidants like
coenzyme Q10, vitamin
E, and idebenone may offer
individuals some limited benefit. However, recent clinical trials in the
United States and Europe
have not revealed effectiveness of
idebenone in people with Friedreich’s ataxia, but more powerful modified
forms of this
agent and other antioxidants are in
trials at this time. There is also a clinical trial to examine the
efficacy of selectively
removing excess iron from the
mitochondria.
Scientists also are exploring ways
to increase frataxin levels through drug treatments, genetic engineering
and protein delivery
systems. Several compounds that are
directed at increasing levels of frataxin may be brought to clinical
trials in the near
future. To check for current trials,
visit
http://www.clinicaltrials.gov. Additional information is available from the groups listed in the following section.
Armed with what they currently know
about frataxin and Friedreich’s ataxia, scientists are working to better
define fraxatin’s
role, clarify how defects in iron
metabolism may be involved in the disease process, and explore new
therapeutic approaches
for therapy.
A lot to read there i know, had to get this out to the masses that don't know. This is Friedreich’s ataxia this is what i live with every day.
