Friedreich ataxia is an autosomal recessive disorder resulting in progressive neurologic and cardiac sequelae. It leads to significant morbidity as well as death.
While the age of onset varies from one individual to another, it usually occurs around puberty . However, there are individuals in which FA presents much earlier or later  . Cases with early onset are associated with larger triplet nucleotide expansions. These patients exhibit rapid deterioration and manifest with cardiac involvement, diabetes, scoliosis and pes cavus . However, those with later onset exhibit less GAA expansions and undergo slower progression .
The earliest feature of the disease is typically the gait ataxia, which results from poor muscle coordination. Both extremities are equally affected. Furthermore, patients with initial unilateral involvement eventually develop generalized ataxia. Some will experience a febrile illness prior to the onset of ataxia. The gait instability is characterized by a wide gait, difficulty with maintaining balance, slow ambulation, and trouble with running and standing. Additionally, patients with steppage gait exhibit uneven contact between the feet and the floor.
Progression of the condition results in extremity and trunk involvement. With ataxia of the arms, action and intention tremors occur. Furthermore, lower extremities become weaker and fatigued, especially in advanced disease states. Abnormal curvature of the spine and foot deformities also occur. Ultimately, patients will require a wheelchair for mobility. Affected facial and buccal muscles produce tremors and choreiform movements. Moreover, an involvement of the muscles in mouth and throat features difficulty with speech and swallowing. Over 50% of FA patients will develop cardiomyopathy and other sequelae such as cardiac arrhythmias and diabetes.
Almost 25% of patients will develop FA after the age of 25. These individuals display an atypical clinical picture consisting of slow progression. Late onset FA occurs between 26 to 39 years while the very late onset presents after 40 years of age. Older onset patients are frequently associated with a subtype called Friedrich ataxia with retained reflex (FARR), in which the tendon reflexes are preserved for up to a decade after onset. FARR a is observed in 12% of FA cases.
The workup consists of a thorough history, physical exam, genetic testing, imaging modalities, and nerve conduction studies. Genetic testing will affirm the diagnosis by locating the FXN gene mutation. MRI of the brain and spinal cord is the test of choice, as it assesses the atrophy observed in FA. Additionally, transcranial sonography is a noninvasive evaluation of cerebellar and other abnormalities. It reveals echogenicity of the dentate in FA patients .
Regarding cardiac studies, echocardiography demonstrates concentric ventricular hypertrophy in FA patients with cardiac involvement. Also, EKG may display ventricular hypertrophy and T wave inversion.
Nerve conduction tests are useful in diagnosing FA. Nerve conduction velocity (NCV) is normal or slightly decreased in these patients. Furthermore, sensory nerve action potentials (SNAP) are nonexistent in over 90% of cases while the remainder exhibit a decrease in the amplitude of potentials. Another study, brainstem auditory evoked responses, are abnormal as well. This reflects the involvement of the auditory pathways.
The therapy of FA is symptomatic and supportive. The multidisciplinary approach focuses on the systems involved. In patients with cardiac manifestations, antiarrhythmics, and drugs geared toward improving heart failure are useful. For those with diabetes, glycemic control through dietary modifications and medications such as oral hypoglycemic drugs and insulin may be appropriate. Patients with a physical handicap may benefit from physical therapy, wheelchairs, prosthesis, and walking aids. Those with scoliosis and foot abnormalities may require surgical intervention. Importantly, consultation with a neurologist and an orthopedic surgeon can guide the medical decision-making process.
For individuals with visual and hearing impairments, corrective devices and medications may be helpful. Speech and swallowing therapy may be indicated in certain patients. Finally, other supportive measures include psychological counseling.
Surveillance is important for all FA patients since they are at risk of developing complications such as heart disease and diabetes. Genetic counseling is recommended for patients and their family members. This service offers information about the inheritance pattern, the probability of having further affected offspring, and genetic testing.
This progressive disorder is associated with poor prognosis. Specifically, patients typically survive until 25 to 30 years of age. Those that live beyond do not have cardiac involvement. In fact, approximately two-thirds of individuals with FA die from cardiac causes such as congestive heart failure and arrhythmias. Therefore, all individuals with FA should be monitored for cardiac manifestations . The quality of life is affected by severe disability and morbidity. Within 15 years of onset, the patients suffer from ambulation difficulties. In particular, almost all become wheelchair bound by the age of 45 years.
FA occurs secondary to an expanded trinucleotide repeat located in the FXN gene. Hence, the impaired gene transcription causes a deficiency in the FXN protein  , which results in iron overload and mitochondrial dysfunction.
This mutation is inherited through an autosomal recessive pattern. Consanguineous unions are associated with a high risk of producing offspring with this recessive disorder. Furthermore, an affected parent (who is not in a consanguineous relationship) exhibits a risk of 1 in 200.
FA is the most common ataxia attributed to recessive inheritance. In fact, it is responsible for half of all cases of inherited ataxia. With regards to the incidence, the estimates range from 1 in 22,000 to 1 in 50,000. The prevalence is 1 in 40,000. The patient demographics reflect a race preference. FA is more common in Europeans and North Americans with European ancestry. It does not occur in black Africans or Asians.
The age of onset is also significant. Specifically, FA manifests in ages ranging from 8 to 15 years of age with the mean age reported as 10.5 plus or minus 7 years . In fact, the nature of the mutation decides when the disease presents  . There is no gender preference.
The pathogenesis of FA exhibits the "dying back phenomena" of axons resulting in the loss of large myelinated axons as well as secondary gliosis. These are mainly observed in the spinal cord and spinal roots. Specifically, the depletion of myelinated axons is occurring in the posterior columns, and the corticospinal and spinocerebellar tracts. Overall, the spinal cord becomes thin and the dorsal spinal ganglia shrink.
Different neuronal types are prone to pathologic changes and each contributes to clinical manifestations . For example, the atrophy of dorsal root ganglia causes peripheral neuropathy while the depletion of large axons in the posterior columns explains the deficits of the position and vibration senses. Since the lateral and ventral spinocerebellar tracts, dentate nucleus, and other close pathways are affected, cerebellar ataxia and abnormalities in proprioception manifest.
Furthermore, corticospinal tracts beyond the cervicomedullay junction are markedly degenerated, and this reflects the typical bilateral extensor plantar responses as well as the weakness experienced in advanced states. Additionally, the loss of large neurons in the sensory ganglia accounts for the absence of tendon reflexes.
The atrophied nuclei of cranial nerves VII, X, and XII result in facial weakness and difficulties in swallowing and speaking. Cardiac muscle fibers demonstrate degeneration as well. The sequelae, chronic interstitial myocarditis, develops as the fibers undergo fibrosis.
Since this an inherited disease, it is not preventable. However, genetic counseling for those with FA provides information on the probability of passing the mutation to future children as well as other relevant details. Also, individuals with an affected family member may be offered genetic testing.
Friedreich ataxia (FA) is a hereditary disease caused by a trinucleotide GAA repeat in the mutated FXN gene, which codes for the mitochondrial protein known as frataxin. This autosomal recessive disorder is characterized by progressive degeneration of the nervous system and the heart , resulting in severe morbidity and mortality. Cardiac complications such as congestive heart failure and arrhythmias account for the latter.
The age of onset is typically around puberty but ranges from 8 to 15 years. This disease is most prevalent in Europeans and individuals of European descent. Due to the neuronal loss of the spinal cord and important sensory pathways, the patients present with a myriad of features. Specifically, individuals with FA display gait instability, progressive ataxia, paresis, dysarthria, and dysphagia. Additionally, these patients exhibit a loss of reflexes and vibratory and position senses. Many will also develop foot deformities, scoliosis, and cardiomyopathy.
Diagnosis is confirmed through genetic testing in addition to a detailed history and physical exam. Imaging modalities and nerve conduction tests are also beneficial. Therapy consists of a multidisciplinary approach towards cardiac manifestations and diabetes as well as correction and improvement of the disabilities. Patients should also undergo close surveillance for heart complications.
Freidrich ataxia (FA) is named after the doctor that first wrote about the disease in 1863. It results from a specific mutation or change in the DNA. Also, FA is inherited in an autosomal recessive pattern. This means that an affected individual inherited a bad copy of the gene from each parent. It is more commonly found in Europeans and North Americans with European ancestry. This disease develops between the ages of 5 and 15 although it can occur at younger and older ages as well. It is typically milder in older ages.
This disorder causes loss and deterioration of the nerve cells in the brainstem and spinal cord. Therefore, patients will experience difficulty with coordination, balance, walking, standing, and running. They also lose the sense of position and reflexes. Additionally, they experience difficulty with speaking and swallowing. Some of the other features include heart diseases and diabetes. These patients can develop heart failure and abnormal heart rhythms resulting in death. Due to the progressive weakness, trouble with walking, deformities of the foot (clubfoot), and scoliosis, patients usually become confined to a wheelchair by the age of 25.
Diagnosis occurs with the doctor obtaining a detailed history, physical exam, and genetic testing. Also, an MRI of the brain and spinal cord may be helpful. Since the heart is often affected, an ultrasound of this organ called echocardiogram can show heart failure and thickening of the left ventricle. Since these patients can have abnormal heart rhythms, they should have EKG testing. Other studies will evaluate the nerve conduction.
The treatment focuses on the heart symptoms, diabetes, and the physical handicaps. For example, antiarrhythmics are important for those with dangerous heart rhythm patterns while patients with heart failure require specific therapy as well. Diabetes is treated with diet modification and medications if needed. As for the physical troubles, wheelchairs, walking aids, physical therapy, and other resources may be necessary. Since this disease takes an emotional toll on patients and their family members, counseling is usually helpful. Genetic counseling can offer patients and their family members very important information about the disease and how it is inherited. A family member can opt for testing as well.