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.

Friedreich's ataxia

 [frēd´rīks]

hereditary sclerosis of the dorsal and lateral columns of the spinal cord, usually beginning in childhood or youth. It is attended by ataxia, speech impairment, scoliosis, and peculiar swaying and irregular movements, with paralysis of the muscles, especially of the lower extremities.

Friedreich's ataxia

[frēd′rīshs]

Etymology: Nikolaus Friedreich, German physician, 1825-1882

a condition characterized by muscular weakness, loss of muscular control, weakness of the lower extremities, and an abnormal gait. It may be hereditary and exhibits both dominant and recessive inheritance patterns. The primary pathological feature is pronounced sclerosis of the posterior columns of the spinal cord with possible involvement of the spinocerebellar tracts and the corticospinal tracts. Friedreich's ataxia usually affects individuals between 5 and 20 years of age. The highest incidence of onset is at puberty. The characteristically ataxic gait may progress to severe disability. Over a period of years a child who is affected may also have ataxia of the upper extremities and difficulty in performing simple maneuvers such as writing or handling eating utensils. The characteristic gait of this disease is caused by a cavus deformity, or clawfoot. The gait and the stance of the affected individual are unsteady. A positive Romberg's sign may be evident, and Babinski's sign is present with absent or decreased deep reflexes. The condition may also cause slurred speech, head tremors, tachycardia, and cardiac failure. Thoracic scoliosis is present in approximately 80% to 90% of the patients afflicted. All the signs and symptoms are progressive. There is no cure. Treatment is supportive. Orthoses may be useful to varying degrees in prevention of associated deformities and maintenance of an ambulatory status. Correction of the foot deformity allows the patient to remain ambulatory as long as possible and is performed when the disease process does not appear to be progressing, thereby reducing the potential for recurrence. Spinal fusion may correct the associated scoliosis. In progression of this disease, death usually results from myocardial failure.

Friedreich's ataxia

Neurology An AR neurodegenerative disorder, which is the most common–prevalence in European stock is ±1:50,000— cause of hereditary ataxia Clinical Ataxia of all limbs, cerebellar dysarthria, absent reflexes in legs, sensory loss, pyramidal signs; onset up to age 25; skeletal deformities and cardiomyopathy are found in most Pts, as are impaired glucose tolerance and DM. See Ataxia.

Friedreich's ataxia

An inherited disorder of the cerebellum and spinal cord causing unsteady gait (ataxia), defective movement of the upper limbs, defective speech, and loss of sensation. The spine becomes bent sideways (scoliosis), the feet become arched (pes cavus) and the heart muscle is damaged. The condition appears first in childhood or adolescence and cases vary greatly in severity. There is no effective treatment. (Nikolas Friedreich, 1826–82, German physician).

hereditary spinal ataxia

; hereditary spinocerebellar ataxia; Friedreich's ataxia inherited autosomal-recessive disease characterized by progressive loss of voluntary muscle coordination; symptoms develop between ages 5 and 15 years, e.g. loss of vibrational and positional awareness, loss of deep tendon reflexes and an extensor plantar response, progressing to loss of voluntary muscle function, pes cavus, wide-based, high-steppage, unsteady ataxic gait, constant unsteadiness and difficulty with standing; 50% develop cardiac disease; 10% develop diabetes mellitus; usually fatal within 15 years of diagnosis

ataxia, hereditary spinal 

A hereditary degeneration of the posterior and lateral columns of the spinal cord occurring in childhood. It is characterized by general ataxia, nystagmus and, sometimes, ptosis and external ophthalmoplegia. Syn. Friedreich's ataxia.