Friedreichs Ataxia

Friedeich's Ataxia

Friedreich’s ataxia (FA or FRDA) is a rare genetic disease caused by a mutation on chromosome 9.  The name is from the German doctor Nicholaus Friedreich who has first described the disease in the 1860s. 

Pathophysiology

Friedreich’s ataxia is caused by a mutation in a gene called Frataxin (FXN) that is found on chromosome 9, leading to too may DNA repeats of GAA.  Those affected with this disease have as many as 1,000 copies of this gene, while normal individuals only have 8 to 30 copies.  This causes a decrease in the production of fraxatin which helps the cells of the body protect itself from free radicals, which cause damage to the cells.  When these free radicals build up inside the cells, cell destruction occurs, leading to the long-term effects or complications of this condition.

This condition mostly affects the nerve cells at the spinal cord and spinal roots, causing thinning and deterioration over time.  The heart muscle fibers also become affected by showing degeneration, followed by swelling and enlarging, leading to heart disease.  Other affected organs are the spine, pancreas, and several cranial nerves. 

Signs and Symptoms

The onset of Friedreich’s ataxia is usually from ages 8 to 15 years, although there are some cases when they appear in adulthood. 

The most common presenting symptom is gait ataxia or difficulty in walking.  There is progressively slow and clumsy walking, difficulty standing and running.  Both lower extremities are equally affected initially, then slowly worsens and affects the trunk and arms.  The arms tend to develop tremors and facial and arm muscles become tremulous.  There is also loss of sensation and loss of knee and ankle tendon reflexes.  With advanced disease, slurred and incomprehensible speech and difficulty swallowing may develop due to weakness of the muscles. 

Scoliosis or a curving of the spine to one side is a common finding in these patients and may tend to be severe, sometimes necessitating surgical intervention. 

Heart disease is also common in FA patients, taking in the form of hypertrophic cardiomyopathy, myocarditis, tachycardia, heart blocks, and progressive cardiac failure.  Symptoms can be palpitations, shortness of breath, and chest pain. 

Some patients develop diabetes mellitus or impaired glucose intolerance as a result of carbohydrate intolerance.

Most of the time, it is those patients with the highest number of GAA repetitions who has the earlier onset and more severe symptoms.

Workup

Aside from the thorough medical history and physical examination, genetic testing can provide confirmation of the diagnosis.  Magnetic resonance imaging (MRI) provides brain and spinal cord images of the atrophy or degeneration involving the cervical spinal cord.  Echocardiography shows heart enlargement and the heart motion.  The electrocardiogram (ECG) reveals the electrical activity of the heart, oftentimes show abnormalities in patients with FA.  Nerve conduction velocity (NCV) studies usually show normal or slightly reduced velocities, reflecting the transmission of the nerve impulses.  Other tests that may be done are Brainstem auditory evoked responses (BAER), Somatosensory evoked potentials (SSEP), and Sensory nerve action potentials (SNAP).

The International Cooperative Ataxia Rating Scale is a scoring system from the World Federation of Neurology that can be used to assess an FA patient’s functions and disturbances in terms of posture and gait, kinetics or movement and coordination, speech, and oculomotor or eye movements.

Treatment

There is currently no cure or prevention for Friedreich’s ataxia.  In a study by Wessel, patients who had received long-term treatment of 5-hydroxytryptophan had a stabilization of posture as compared with those who had not received the treatment.  Studies for the benefits of Coenzyme Q are currently being made to determine its effect on cardiac function. 

Treatment is aimed at alleviating the symptoms of the complications.  Standard treatments are given for diabetes and heart disease.  Braces or surgery can be performed to correct bony deformities like scoliosis.  Physical and occupational therapy may help with the use of the arms and legs. 

Written by Dr. Karla Torio, MD.

References:

http://emedicine.medscape.com/article/1150420-overview

http://www.umm.edu/ency/article/001411.htm

http://www.intelihealth.com/IH/ihtIH/c/9339/11087.html

Schmitz-Hubsch T, et al. Mov Disord 2006; 21(5):699-704.

Trouillas P.  J Nerol Sci 1997; 145(2):205-11.

Storey E. Mov Disord 2004; 19(2):190-2

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