While the age of onset varies from one individual to another, it usually occurs around puberty [4]. However, there are individuals in which FA presents much earlier or later [5] [8]. 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 [9]. However, those with later onset exhibit less GAA expansions and undergo slower progression [9]. 

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. 

Atypical presentation

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. 

• Falling

  Although the patient's gait remained significantly impaired, extended use of the U-Step Walking Stabilizer modestly improved her gait performance, and her rate of falls decreased from 10 to 3 per month. [ncbi.nlm.nih.gov]

  He is thinking about quitting his soccer team since he is embarrassed by his frequent falls when his legs sometimes “give out” under him. He was diagnosed with scoliosis by his school nurse last month. [osmosis.org]

  Patients reported that their major transitions were the recognition of symptoms, fear of falling, inability to do usual tasks, and need of assistive devices. [movementdisorders.org]

  […] particularly color vision Decrease in ability to feel vibrations in lower limbs Foot problems, such as hammer toe and high arches Hearing loss, this occurs in about 10% of people Jerky eye movements Loss of coordination and balance, which leads to frequent falls [medlineplus.gov]

• Difficulty Walking

  If you notice any of the symptoms mentioned, such as loss of sensation, difficulty walking, keeping your balance, or a loss of reflexes, ask your doctor about FA. [columbianeurology.org]

  Specific symptoms include Difficulty walking Muscle weakness Speech problems Involuntary eye movements Scoliosis (curving of the spine to one side) Heart palpitations, from the heart disease which can happen along with Friedreich's ataxia People with [medlineplus.gov]

  Difficulty walking The legs can be affected in different ways by Friedreich’s ataxia, including muscle weakness, weak or lack of leg reflexes, poor coordination and balance, foot deformities, and not being able to sense vibrations in the lower limbs, [friedreichsataxianews.com]

• Wheelchair Bound

  Trinucleotide expansion length was determined and lymphocyte frataxin levels measured. p.R165P mutation carriers became wheelchair bound early, but had retained reflexes, better arm function, milder dysarthria, and were more independent in activities [ncbi.nlm.nih.gov]

  bound by the age of fifteen. [codyestepwordpresscom.wordpress.com]

  About ten years after the onset of the first symptoms, those affected usually become wheelchair-bound. Life expectancy is severely reduced, above all when there are serious secondary complications, such as progressive cardiomyopathy. [irbbarcelona.org]

• Congestive Heart Failure

  Congestive heart failure usually is a terminal event. [ncbi.nlm.nih.gov]

  Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. [hon.ch]

  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. [symptoma.com]

  Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy ), and lower extremity weakness. [expertscape.com]

• Collapse

  The collapse of the DN is especially apparent after a macroscopic iron stain ( Fig. 3 ). [ncbi.nlm.nih.gov]

  He had a daughter, Mireille, with a French woman – the relationship collapsed soon after – and in 1949 married another, Marie-Josèphe Dublé, with whom he had a son. [lrb.co.uk]

• Abnormal Eye Movement

  As the disease gets worse, people may develop bony deformities of the spine and feet, loss of sensation in the limbs, speech problems, abnormal eye movements, heart disease and diabetes. [health.harvard.edu]

  Individuals with FA often have abnormal eye movements (called nystagmus ) and some may develop hearing and visual loss. [cafamily.org.uk]

  Results The most frequent clinical features beyond afferent ataxia were abnormal eye movements (90.5%), scoliosis (73.5%), deformities of the feet (58.8%), urinary dysfunction (42.8%), cardiomyopathy and cardiac hypertrophy (40.3%), followed by decreased [n.neurology.org]

• Foot Deformity

  Omaveloxolone produced greater improvements in mFARS in patients that did not have musculoskeletal foot deformity (pes cavus). [ncbi.nlm.nih.gov]

  Orthopedic problems such as foot deformities and scoliosis can be treated with braces or surgery. Rehabilitative therapy (physical, occupational, and vocational) can help individuals become as functionally independent as possible. [ninds.nih.gov]

  Management of Foot Deformities[edit | edit source] The foot deformities associated with FA can exacerbate gait abnormalities and unsteadiness. [physio-pedia.com]

• Muscular Atrophy

  atrophy and related syndromes G12.0 Infantile spinal muscular atrophy, type I [Werdnig-Hoffman] G12.1 Other inherited spinal muscular atrophy G12.2 Motor neuron disease Reimbursement claims with a date of service on or after October 1, 2015 require the [icd10data.com]

  The Ryukyan muscular atrophy. An obscure heritable neuromuscular disease found in the inseln of southern Japan J Neurol Sci. 1970; 11: 359-382. Přejít k původnímu zdroji... McDermott CJ, White K, Buthley K, et al. [solen.cz]

• Ataxia

  Friedreich ataxia (FA) is the most common inherited progressive ataxia. It carries an autosomal recessive inheritance 1. Thought to have an estimated prevalence of ~1:50,000. There is no recognized gender predilection. [radiopaedia.org]

  Although rare, Friedreich’s ataxia is the most common form of hereditary ataxia, affecting about one in every 50,000 people in the United States. [medicalmarijuana.com]

  Summary of Friedreich's ataxia Friedreich's ataxia Friedreich's ataxia is an autosomal recessive inherited disease that causes progressive damage to the nervous system. [osmosis.org]

  Scale for the Assessment and Rating of Ataxia (SARA): similar scale to the ICARS to assess ataxia but shorter to administer. Friedreich’s Ataxia Rating Scale (FARA): assessment for ataxia specific to FA. [physio-pedia.com]

  OBJECTIVE To describe the phenotype of Friedreich's ataxia cardiomyopathy and distinguish stages of disease progression. METHODS 32 consecutive patients with genetically confirmed Friedreich's ataxia were included. [escardio.org]

• Dysarthria

  Abstract Patterns of dysarthria in spinocerebellar ataxias (SCAs) and their discriminative features still remain elusive. Here we aimed to compare dysarthria profiles of patients with (SCA3 and SCA6 vs. [ncbi.nlm.nih.gov]

• Cerebellar Ataxia

  Equistasi may improve limb and gait ataxia – a loss of control of voluntary muscular movement – in patients with hereditary cerebellar ataxia, such as Friedreich’s ataxia, although more studies are necessary to confirm these findings. [equistasi.com]

  A clinical analysis of patients with early-onset cerebellar ataxia and retained reflexes suggested that they differed from patients with Friedreich's ataxia by the absence of cardiomyopathy and optic atrophy, 6 the presence of cerebellar atrophy on magnetic [doi.org]

  G11.0 Congenital nonprogressive ataxia G11.1 Early-onset cerebellar ataxia G11.2 Late-onset cerebellar ataxia G11.3 Cerebellar ataxia with defective DNA repair G11.4 Hereditary spastic paraplegia G11.8 Other hereditary ataxias G11.9 Hereditary ataxia [icd10data.com]

• Nystagmus

  11 36.7 Asymmetrical optokinetic nystagmus 10 33.4 Spontaneous nystagmus 6 20.0 Pendulum tracking alterations 5 16.7 Bilateral labyrinthine hyperreflexia 5 16.7 Bidirectional semi-spontaneous nystagmus 2 6.7 Unidirectional semi-spontaneous nystagmus [scielo.br]

  The ataxia is accompanied by vertigo, nausea and nystagmus. Cerebellar Ataxia: It occurs when the cerebellum or its connections are affected. Ataxia of the trunk and extremities, and dysarthria and nystagmus are present. [fizikon.com]

  The clinical picture consisted of progressive spastic gait, truncal and limb ataxia, dysarthria, nystagmus, hyperreflexia with knee and ankle clonus and extensor plantar response, and mild hypopallesthesia. Ages at present vary between 50 and 59. [ncbi.nlm.nih.gov]

  HEENT showed pupils to be equal, round and reactive to light and accommodation and no nystagmus. Visual acuity was 20/30 bilaterally. Thyroid was normal size without masses. Lungs, heart, and abdomen were normal. She was Tanner 2 for breast. [pediatriceducation.org]

• Tremor

  Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. [hon.ch]

  As the disease progresses, limb incoordination, dysmetria (lack of coordination of movements characterized by under- or over-shooting intended position) and intention tremor (a tremor that is triggered by aiming for a particular location) follow. [themedicalbiochemistrypage.org]

  Symptoms range from the inability to coordinate movements to gait instability with imbalance, muscle weakness and tremors. Patients lose their ability to stand, sit and walk within 10 – 15 years of onset. [minoryx.com]

  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. [symptoma.com]

  Other difficulties include constant tremor, slurred speech, difficulty swallowing, scoliosis, heart abnormalities and diabetes. Onset of symptoms can vary from childhood to adulthood. [faraireland.ie]

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 [10]. 

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 [7]. 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 [1] [2], 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 [3]. In fact, the nature of the mutation decides when the disease presents [4] [5]. 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 [6]. 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 [1], 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. 

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3. Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996; 271(5254): 1423-7.
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