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| DiseaseID |
HGD15 |
| Genetic
Disorder |
Friedreich's ataxia
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| Gene
Name |
frataxin (FXN)gene |
| Description |
Friedreich's ataxia (FRDA) is a rare inherited disease characterized by the progressive loss of voluntary muscular coordination (ataxia) and heart enlargement. It is named after the German doctor, Nikolaus Friedreich, who first described the disease in 1863. FRDA is generally diagnosed in childhood and affects both males and females.
FRDA is an autosomal recessive disease caused by a mutation of a gene called frataxin, which is located on chromosome 9. This mutation means that there are many extra copies of a DNA segment, the trinucleotide GAA. A normal individual has 8 to 30 copies of this trinucleotide, while FRDA patients have as many as 1000. The larger the number of GAA copies, the earlier the onset of the disease and the quicker the decline of the patient.
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| Symptoms |
Symptoms are caused by the wearing away of structures in areas of the brain and spinal cord that control coordination, muscle movement, and some sensory functions. Symptoms generally begin in childhood before puberty, and may include:
• Unsteady gait and uncoordinated movements (ataxia) -- gets worse with time
• No reflexes in the legs
• Abnormal speech
• Loss of coordination and balance, which leads to frequent falls
• Decrease in ability to feel vibrations in lower limbs
• Muscle weakness
• Changes in vision, particularly color vision
• Hearing loss -- occurs in about 10% of patients
• Jerky eye movements
• Foot problems, such as hammer toe and high arches
Muscle problems lead to changes in the spine, which may result in scoliosis or kyphoscoliosis.
Heart disease usually develops and may lead to heart failure. Death may result from heart failure or dysrhythmias that do not respond to treatment. Diabetes may develop in later stages of the disease.
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| Causes |
Friedreich's Ataxia is caused by an abnormality in one of the genes, called X25, located in the ninth chromosome pair. Genes are sets of instructions that tell the cells, containing chromosomes, how to build the proteins that enable these cells to carry out their various functions. These functions determine a person's physical characteristics, from the color of the hair and eyes to the organization of the nervous system.
Friedreich's Ataxia occurs when there is a lack of the protein frataxin (for which X25 provides the code) in the tissues. This lack of protein causes the nerve cells within the tissues of the spinal cord and its brain connections, the heart and pancreas to degenerate, thereby reducing nerve signals to the muscles.
The disorder develops only when a person inherits the defective gene from both parents. This is called a recessive inheritance pattern. If only one parent contributes a defective gene, the child becomes a "carrier" of Friedreich's Ataxia but never develops the disorder.
Carriers appear neurologically normal, and sometimes may not know they are carriers until an afflicted child is born to them. In the United States, it is estimated that 1 out of every 100 people is a carrier of the Friedreich's gene defect, and 1 of every 40,000 is affected with Friedreich's Ataxia. Each child of parents who are both carriers has a 25 percent chance of inheriting the disease. |
| Diagnosis |
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
Tests of the heart may show a condition called hypertrophic cardiomyopathy in about 66% of persons with this condition.
Blood sugar (glucose) tests may reveal diabetes or glucose intolerance. An eye exam may show damage to the optic nerve, which usually occurs without symptoms.
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| Treatment |
Treatment for Friedreich's ataxia includes:
• Counseling
• Speech therapy
• Physical therapy
• Walking aids or wheelchairs
Orthopedic interventions (such as braces) may be needed for scoliosis and foot problems. Treatment of heart disease and diabetes may help improve the quality and duration of life. |
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