Friedreich's Ataxia
Friedreich's ataxia
Definition
Friedreich's ataxia (FA) is an inherited, progressive nervous system disorder causing loss of balance and coordination, speech problems, and heart disease.
Description
FA is an inherited disease marked by impaired coordination that is a result of degeneration of the structures in the cerebellum and the spinal cord, which are responsible for coordination, muscle movement, and some sensory functions, including color vision and hearing. The intellect of a child with FA is normal.
FA is an autosomal recessive disease, which means that two defective gene copies, one from each parent, must be inherited to develop symptoms. A person with only one defective gene copy will not show signs of FA, but may pass along the gene to offspring. Couples with one child affected by FA have a 25 percent chance in each pregnancy of conceiving another affected child.
FA is also referred to as spinocerebellar degeneration.
Demographics
Friedreich's ataxia is the most common inherited ataxia, affecting one in 50,000 people in the United States. Females and males are affected equally.
Causes and symptoms
Causes
The gene for FA codes for a protein called frataxin. Normal frataxin is found in the cellular energy structures known as mitochondria, where it is thought to be involved in regulating the transport of iron. In FA, the frataxin gene on chromosome 9 is expanded when a particular sequence of bases in the DNA is repeated too many times. Ordinarily, there are seven to 22 repeats of the frataxin gene; in FA, this sequence may be repeated between 800 to 1,000 times. This extra DNA interferes with normal production of frataxin, thereby impairing iron transport. The triplet repeat expansion seems to interfere with the normal assembly of amino acids into proteins, significantly reducing the amount of frataxin that is made. Without a normal level of frataxin, some of the body's cells—especially those of the brain, spinal cord, and muscle—cannot handle the normal amounts of "oxidative stress," which the mitochondria produce. When excess iron in the cells (as a result of the deficiency of frataxin) reacts with oxygen, free radicals are produced. Free radicals are necessary molecules in the body's metabolism, but in excess they can also destroy cells and harm the body.
The types of symptoms and severity of FA seems to be associated with the number of repetitions. Children with more copies have more severe symptomatology, with symptoms starting at a younger age.
The nerve cells most affected by FA are those in the spinal cord involved in relaying information between muscles and the brain. Control of movement requires complex feedback between the muscles promoting a movement, those restraining it, and the brain. Without this control, movements become uncoordinated, jerky, and inappropriate to the desired action.
Symptoms
Symptoms of FA usually first appear between the ages of five and 15 years, although onset as early as 18 months or as late as age 30 years is possible. The first symptom is usually gait incoordination. A child with FA may graze doorways when passing through, for instance, or trip over low obstacles. Unsteadiness when standing still and deterioration of position sense is common. Children with FA may develop foot deformities such as club-foot , hammertoe, and high arches. Walking up off the heels often results from uneven muscle weakness in the legs. Muscle spasms and cramps may occur, especially at night. Other early symptoms include changes in speech, swallowing difficulties, loss of reflexes, and jerky eye movements (nystagmus ).
Ataxia in the arms follows, usually within several years, leading to decreased hand-eye coordination . Arm weakness does not usually occur until much later. There is often a gradual loss of sensation in the extremities, which may spread to other parts of the body. In about 10 percent of children with FA, diabetes mellitus may develop in the later stages of the disease. Some loss of visual acuity may be noted. Hearing loss occurs in about 10 percent of children with FA, and about 20 percent develop carbohydrate intolerance . A side-to-side curvature of the spine (scoliosis ) occurs in many cases, and may become severe. About 50 percent of people develop problems with control of their urge to urinate (urinary urgency), or become incontinent.
Various forms of heart disease often accompany FA, including cardiomyopathy (enlargement of the heart), myocardial fibrosis (formation of fiber-like materials in heart muscles), and cardiac failure. Symptoms of heart involvement include chest pain , shortness of breath, and heart palpitations. Heartbeat abnormalities such as tachycardia (rapid heart rate) and heart block (impaired conduction of the heart's cardiac impulses) are common occurrences.
When to call the doctor
Any time a child with FA reports unusual heart symptoms, such as shortness of breath on exertion, dizziness , fainting, chest pain or discomfort, or abnormal heart rhythms, the doctor or cardiologist should be called, or the child should be taken immediately to a hospital emergency room.
Diagnosis
Diagnosis of FA involves a careful medical history and thorough neurological exam. Laboratory tests include electromyography (a measurement of the electrical activity of muscle cells) and nerve conduction velocity tests, which measure the speed that nerves transmit impulses. An electrocardiogram and echocardiogram may be performed to diagnose heart disease. Imaging studies are conducted to provide pictures of the brain and spinal cord. A spinal tap is performed to evaluate the cerebrospinal fluid. Blood and urine samples are tested for elevated glucose levels, to determine whether the child has diabetes.
Direct DNA testing is available, allowing FA to be more easily distinguished from other types of ataxia. The same test may be used to determine the presence of the genetic defect in unaffected individuals, such as siblings.
Treatment
There is no cure for FA, nor is there any treatment that can slow its progress. Therefore, the goal of treatment is to control symptoms and maintain general health. Amantadine may provide some limited improvement in ataxic symptoms, but is not recommended in children with cardiac abnormalities. Physical therapy and activity are used to maintain range of motion in weakened muscles and to compensate for loss of coordination and strength. Some children find that using weights on the arms can help dampen the worst of the uncoordinated arm movements. Scoliosis and foot deformities can be treated with braces or surgery.
Safety is an important consideration in this disease since the child will eventually experience loss of balance and sensation. Occupational therapy is recommended to select adaptive techniques and devices such as safety railings, walkers, or other safety appliances. If the child loses feelings in various body parts, injuries can be avoided by testing bath water to prevent burns , inspecting the body visually for injuries, and using protective shoes and helmets.
Diabetes is treated with insulin and dietary changes. Some of the heart problems can be treated with medications.
Since the disease may be associated with damage to cells caused by free radicals, antioxidants such as vitamin E and coenzyme Q10 are often prescribed for children with FA.
Prognosis
The rate of progression of FA is highly variable. Most children lose the ability to walk within 15 to 20 years after the onset of symptoms, and will require aids for walking such as scooters, walkers, or wheelchairs. In later stages of the disease, people become incapacitated.
Reduction in lifespan from FA complications is also quite variable. Average age at death is in the mid-thirties, but may be as late as the mid-sixties in persons with less severe symptoms. Many persons with FA will develop untreatable heart disease, which may shorten life expectancy.
Prevention
There is no way to prevent development of FA in a person carrying two defective gene copies. Genetic counseling and testing are recommended for prospective parents with a family history of FA.
Parental concerns
Coping with the challenges of raising a child with a chronic serious disease is difficult for parents and other family members. Psychological counseling and support groups are invaluable tools to help families meet the challenges and provide the child with needed support.
A child with Friedreich's ataxia is entitled to an Individual Education Plan (IEP) through the Individuals with Disabilities Education Act (IDEA). An IEP team consisting of parents, administrators, teachers, and sometimes the student and outside experts, will collaborate to develop the child's IEP.
Children with FA are considered high-risk for flu and pneumonia . The children and family members should receive a flu shot every year, unless there are other health considerations that would indicate that there is a reason not to receive the vaccine. The children should also periodically receive pneumococcal pneumonia shots as recommended by their doctors.
KEY TERMS
Ataxia —A condition marked by impaired muscular coordination, most frequently resulting from disorders in the brain or spinal cord.
Oxidative stress —A condition where the body is producing an excess of oxygen-free radicals.
Scoliosis —An abnormal, side-to-side curvature of the spine.
See also Movement disorders.
Resources
BOOKS
Feldman, Eva L. "Hereditary Cerebellar Ataxias and Related Disorders." In Cecil Textbook of Medicine. Eds. Russell L. Cecil et al. Philadelphia: W.B. Saunders Company, 2000.
Icon Health Publications. The Parent's Guide on Friedreich's Ataxia: A Revised and Updated Directory for the Internet Age. San Diego, CA: Icon Health Publications, 2002.
Rieffenberger, Amanda. Through the Eyes of a Child. Available from the author at (605) 882-2343 or at [email protected], 1996.
"Spinocerebellar Degeneration (Friedreich's Ataxia)." In Harrison's Principles of Internal Medicine. Eds. Kurt J. Isselbacher et al. New York: McGraw-Hill, 2001.
ORGANIZATIONS
Friedreich's Ataxia Research Alliance. 2001 Jefferson Davis Hwy, Suite 209, Arlington, VA 22202. (703) 413-4468. Fax: (703) 413-4467. Web site: <www.frda.org>.
Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718-3208. (520) 529-2000 or (800) 572-1717. Fax: 520-529-5300. Web site: <www.mdausa.org>.
National Ataxia Foundation. 2600 Fernbrook Lane, Suite 119, Minneapolis, MN 55447-4752. (763) 553-0020. Web site: <www.ataxia.org>.
National Organization for Rare Disorders (NORD). P.O. Box 1968, 55 Kenosia Avenue, Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-6673. Fax: (203) 798-2291. Web site: <www.rarediseases.org>.
WEB SITES
Friedreich's Ataxia Fact Sheet. Available online at: <www.ninds.nih.gov/health_and_medical/pubs/friedreich_ataxia.htm>.
Friedreich's Ataxia Parents Group (FAPG). Available online at: <www.fortnet.org/fapg/>.
Judith Sims Rosalyn Carson-DeWitt, M.D.
Friedreich's Ataxia
Friedreich's Ataxia
Definition
Friedreich's ataxia (FA) is an inherited, progressive nervous system disorder causing loss of balance and coordination.
Description
Ataxia is a condition marked by impaired coordination. Friedreich's ataxia is the most common inherited ataxia, affecting between 3,000-5,000 people in the United States. FA is an autosomal recessive disease, which means that two defective gene copies must be inherited to develop symptoms, one from each parent. A person with only one defective gene copy will not show signs of FA, but may pass along the gene to offspring. Couples with one child affected by FA have a 25% chance in each pregnancy of conceiving another affected child.
Causes and symptoms
Causes
The gene for FA codes for a protein called frataxin. Normal frataxin is found in the cellular energy structures known as mitochondria, where it is thought to be involved in regulating the transport of iron. In FA, the frataxin gene on chromosome 9 is expanded with nonsense information known as a "triple repeat." This extra DNA interferes with normal production of frataxin, thereby impairing iron transport. Normally, there are 10-21 repeats of the frataxin gene. In FA, this sequence may be repeated between 200-900 times. The types of symptoms and severity of FA seems to be associated with the number of repetitions. Patients with more copies have more severe symptomatology. Researchers are still wrestling with how frataxin and the repeats on chromosome 9 are involved in causing FA. One theory suggests that FA develops in part because defects in iron transport prevent efficient use of cellular energy supplies.
The nerve cells most affected by FA are those in the spinal cord involved in relaying information between muscles and the brain. Tight control of movement requires complex feedback between the muscles promoting a movement, those restraining it, and the brain. Without this control, movements become uncoordinated, jerky, and inappropriate to the desired action.
Symptoms
Symptoms of FA usually first appear between the ages of 8 and 15, although onset as early as 18 months or as late as age 25 is possible. The first symptom is usually gait incoordination. A child with FA may graze doorways when passing through, for instance, or trip over low obstacles. Unsteadiness when standing still and deterioration of position sense is common. Foot deformities and walking up off the heels often results from uneven muscle weakness in the legs. Muscle spasms and cramps may occur, especially at night.
Ataxia in the arms follows, usually within several years, leading to decreased hand-eye coordination. Arm weakness does not usually occur until much later. Speech and swallowing difficulties are common. Diabetes mellitus may also occur. Nystagmus, or eye tremor, is common, along with some loss of visual acuity. Hearing loss may also occur. A side-to-side curvature of the spine (scoliosis ) occurs in many cases, and may become severe.
Heartbeat abnormalities occur in about two thirds of FA patients, leading to shortness of breath after exertion, swelling in the lower limbs, and frequent complaints of cold feet.
Diagnosis
Diagnosis of FA involves a careful medical history and thorough neurological exam. Lab tests include electromyography, an electrical test of muscle, and a nerve conduction velocity test. An electrocardiogram may be performed to diagnose heart arrhythmia.
Direct DNA testing is available, allowing FA to be more easily distinguished from other types of ataxia. The same test may be used to determine the presence of the genetic defect in unaffected individuals, such as siblings.
Treatment
There is no cure for FA, nor any treatment that can slow its progress. Amantadine may provide some limited improvement in ataxic symptoms, but is not recommended in patients with cardiac abnormalities. Physical and occupational therapy are used to maintain range of motion in weakened muscles, and to design adaptive techniques and devices to compensate for loss of coordination and strength. Some patients find that using weights on the arms can help dampen the worst of the uncoordinated arm movements.
Heart arrhythmias and diabetes are treated with drugs specific to those conditions.
Prognosis
The rate of progression of FA is highly variable. Most patients lose the ability to walk within 15 years of symptom onset, and 95% require a wheelchair for mobility by age 45. Reduction in lifespan from FA complications is also quite variable. Average age at death is in the mid-thirties, but may be as late as the mid-sixties. As of mid-1998, the particular length of the triple repeat has not been correlated strongly enough with disease progression to allow prediction of the course of the disease on this basis.
Prevention
There is no way to prevent development of FA in a person carrying two defective gene copies.
Resources
BOOKS
Feldman, Eva L. "Hereditary Cerebellar Ataxias and Related Disorders." In Cecil Textbook of Medicine, edited by Russel L. Cecil, et al. Philadelphia: W.B. Saunders Company, 2000.
Isselbacher, Kurt J., et al. "Spinocerebellar Degeneration (Friedreich's Ataxia)." In Harrison's Principles of Internal Medicine. New York: McGraw-Hill, 2001.
ORGANIZATIONS
Muscular Dystrophy Association. 3300 East Sunrise Drive, Tucson, AZ 85718. (520) 529-2000 or (800) 572-1717. 〈http://www.mdausa.org〉.
KEY TERMS
Ataxia— A condition marked by impaired coordination.
Scoliosis— An abnormal, side-to-side curvature of the spine.