Friedreich's ataxia

Definition

Friedreich's ataxia (FRDA) is a rare inherited disease. The two main features of this disorder are:

• progressive loss of voluntary muscular coordination (ataxia)
• heart enlargement

Diagnosis is usually made between ages 8 and 15, and for most by age 25.

Causes, incidence, and risk factors

Friedreich's ataxia is an autosomal recessive genetic disorder, meaning the affected individual must inherit two altered genes - one from the mother and one from the father.

A gene called Frataxin (FXN), located on chromosome 9, is involved. Changes in the gene result in many extra copies of a DNA segment called a trinucleotide repeat (GAA). Individuals without Friedreich ataxia have anywhere from 8 to 30 copies of this GAA segment. Individuals with FRDA have as many as 1,000 copies. The more copies of GAA the individual has, the earlier the onset of the disease and the faster it progresses.

Incidence is 1 in 22,000-29,000 and risk factors include family history.

Symptoms

• Unsteady gait and uncoordinated movements (ataxia) that gets progressively worse
• Absent reflexes in the legs
• Onset before age 25
• Abnormal speech (dysarthria)
• Loss of coordination and balance; frequent falls or falling more than usual
• Decrease in vibration sense in lower limbs
• Muscle weakness (decreased muscle strength, independent of exercise)
• Autosomal recessive inheritance

Note: The intellect is normal.

Symptoms are caused by degeneration of structures in the cerebellum and spinal cord responsible for coordination, muscle movement, and some sensory functions. Vision, particularly color vision, is often mildly affected. Hearing loss occurs in about 10% of patients.

Symptoms generally begin in childhood before puberty. Early symptoms include an unsteady gait, changes in speech, loss of reflexes, and jerky eye movements.

Abnormal muscle control and tone lead to spinal changes and scoliosis, or kyphoscoliosis may develop. Individuals with Friedreich's ataxia may also have hammer toe and high arches.

Heart disease usually develops and may progress into heart failure. Death may result from heart failure or dysrhythmias that will not respond to treatment. Diabetes may develop in later stages of the disease in up to one-third of patients.

Signs and tests

The following tests may be performed:

• ECG
• Genetic testing for the frataxin gene
• X-ray of the chest
• X-ray of the spine
• Electrophysiological studies
• EMG (electromyography)
• Nerve conduction tests
• Muscle biopsy
• X-ray, CT scan, or MRI of the head
• Motor nerve conduction velocity of greater than 40 m/s with reduced or absent sensory nerve action potential
• Hypertrophic cardiomyopathy (detectable in two-thirds of individuals with FRDA)
• Diabetes occurs in 10% of individuals with FRDA, and an additional 20% may have glucose intolerance
• Optic nerve atrophy, often without symptoms, occurs in approximately 25% of individuals with FRDA
• Sensorineural hearing loss occurs in 10% of cases

Treatment

Treatment for FRDA includes psychological support, prostheses, walking aids, wheelchairs, physicial therapy, and speech therapy -- all important for maintaining an active lifestyle. Orthopedic interventions for scoliosis and foot deformities may be necessary. Treatment of associated cardiac disease and diabetes may help improve the quality and duration of life in individuals with FRDA.

Expectations (prognosis)

FRDA is a progressive disorder causing significant problems in daily living. Most patients are confined to a wheelchair within 15 years of disease onset, and 95% will be by age 45. Lifespan is reduced. The expected range is 21-69 years.

Complications

• Loss of mobility
• Heart failure or heart disease
• Diabetes

Calling your health care provider

Call your health care provider if muscle weakness, numbness, loss of coordination, loss of reflexes, or other symptoms of Friedreich's ataxia occur (particularly if there is a family history of the disorder).

Prevention

Individuals with a family history of FRDA who intend to have children should consider genetic counseling to determine their risks.

Illustrations

Central nervous system

Page Content:

Spinocerebellar degeneration ; degeneration spinocerebellar; degeneration disease spinocerebellar