Friedreich ataxia (FRDA) is an autosomal recessive hereditary ataxia that is typically diagnosed in early childhood and was first reported by German physician Nikolaus Friedreich in 1863. Degeneration occurring in Friedreich ataxia is significantly prominent in the peripheral nervous system (PNS). FRDA is considered the most common form of all inherited ataxias known to date accounting for approximately 50% of all ataxia cases. Ataxia is a group of disorders that affect movement, coordination, and balance. FRDA is inherited ataxia of the limbs with gait, and dysarthria (speech disorder) as classical symptoms along with additional complications of heart disease and diabetes mellitus.
FRDA is caused by loss of function mutation in the FXN gene located in the centromeric region of chromosome 9q (9q13-21.1) which codes for the protein frataxin. This is a mitochondrial protein essential for ATP production that also serves to regulate iron stores and prevent oxidative phosphorylation. A decrease in frataxin due to this mutation affects the cell’s ability to produce energy. This condition ultimately results in cell death, particularly of the neurons, cardiomyocytes, and pancreatic beta cells. The most affected parts of the body are the nervous system, heart, skeleton, and pancreas.
FRDA is an autosomal recessive disease in 96% of the cases meaning that a person should have defects on both copies of the chromosomes received from their parents. Approximately 75% of the FRDA patients are less than 25 years of age. The global prevalence of this disease is 1 in 40,000. It mainly occurs in Europe, the Middle East, South Asia (Indian subcontinent), and North Africa, and is most common in people of Western European descent. However, the incidence of FRDA in Asians and those of African descent is very low.
The central and peripheral nervous systems along with the heart and kidneys are damaged in FRDA. The symptoms can be divided into 3 categories:
1. Neurological symptoms
Ataxia, caused by neurodegeneration in the cerebellum, spinal cord, and peripheral sensory nervous system is the most common symptom of FRDA. It also causes difficulties in coordination and balance.
Lower limb areflexia (inability of muscles to produce an involuntary response to a stimulus)
Dysphagia (difficulty in swallowing)
Dysarthria (difficulty in speech)
Overall weakening of muscles
Scoliosis (curvature of the spine to one side)
Foot deformities such as Pes cavus (sole is too much elevated from the ground) and clubfoot (foot is turned inward) are rare symptoms
Certain urological symptoms (related to the urinary system)
2. Visceral symptoms
Cardiac hypertrophy (enlargement of the heart)
3. Psychiatric symptoms
Mild executive dysfunction
A detailed physical examination and evaluation of family history is the first step in the diagnosis of FRDA. Once a diagnosis of FA is suspected, the following tests should be performed:
Genetic Testing- Genetic testing is the mainstay of FRDA diagnosis. Long-range PCR and Triplet repeat primed PCR are effective ways of estimating abnormal GAA triplet sequences, which is the hallmark of the disease.
Imaging- Patients suspected of having FA should undergo magnetic resonance imaging (MRI) of the brain and spinal cord, which shows atrophy of the cervical/thoracic spinal cord and cerebellum.
Other tests include electrocardiogram, auditory testing, and vision testing.
There is still no cure for this disease. Treatment involves the management of symptoms and complications such as diabetes mellitus and heart failure. Physical therapy (PT) is the main recommendation to delay this disease's progression and preserve function. Exercises help patients to maintain functional use of extremities, improve ataxia, and manage scoliosis. Occupational therapy is essential to maintain independence such as transfers, locomotion, “safe fall” strategies, as well as mobility aids. Functional electrical stimulation and transcutaneous nerve stimulation may alleviate gait and spasticity symptoms. Pharmacological treatment is focused primarily on pain management, heart failure, and prevention of infection. Surgery may be required in extreme cases of kyphoscoliosis and foot deformities. Automated implantable cardioverter-defibrillator placement may be preferred based on the clinician’s assessment of the case. The disease demands early genetic testing and subsequent management to attain a better quality of life.