Category Archives: Ataxia

Friedreich's ataxia is an autosomal recessive inherited disease that causes progressive damage to the nervous system. It manifests in initial symptoms of poor coordination such as gait disturbance; it can also lead to scoliosis, heart disease and diabetes, but does not affect cognitive function. The disease progresses until a wheelchair is required for mobility. Its incidence in the general population is roughly 1 in 50,000.

The particular genetic mutation (expansion of an intronic GAA triplet repeat in the FXN gene) leads to reduced expression of the mitochondrial protein frataxin. Over time this deficiency causes the aforementioned damage, as well as frequent fatigue due to effects on cellular metabolism.

The ataxia of Friedreich's ataxia results from the degeneration of nervous tissue in the spinal cord, in particular sensory neurons essential (through connections with the cerebellum) for directing muscle movement of the arms and legs. The spinal cord becomes thinner and nerve cells lose some of their myelin sheath (the insulating covering on some nerve cells that helps conduct nerve impulses).

The condition is named after the German physician Nikolaus Friedreich, who first described it in the 1860s.[1]

Friedreich, working as a professor of pathology at the University of Heidelberg, reported five patients with the condition in a series of three papers in 1863.[2][3][4] Further observations appeared in a subsequent paper in 1876.[5]

Symptoms typically begin sometime between the ages of 5 to 15 years, but in Late Onset FA may occur in the 20s or 30s. Symptoms include any combination, but not necessarily all, of the following:

It presents before 25 years of age with progressive staggering or stumbling gait and frequent falling. Lower extremities are more severely involved. The symptoms are slow and progressive. Long-term observation shows that many patients reach a plateau in symptoms in the patient's early adulthood. On average, after 1015 years with the disease, patients are usually wheelchair bound and require assistance with all activities of daily living.[7]

The following physical signs may be detected on physical examination:

20% of cases are found in association with diabetes mellitus.[6]

Friedreich's ataxia is an autosomal recessive disorder that occurs when the FXN gene contains amplified intronic GAA repeats. The FXN gene encodes the protein frataxin.[8] GAA repeat expansion causes frataxin levels to be reduced. Frataxin is an iron-binding protein responsible for forming ironsulphur clusters. One result of frataxin deficiency is mitochondrial iron overload which can cause damage to many proteins.[8] The exact role of frataxin in normal physiology remains unclear.[9] The gene is located on chromosome 9.

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Friedreich's ataxia - Wikipedia, the free encyclopedia

Friedreich's ataxia (also called FA or FRDA) is a rare inherited disease that causes nervous system damage and movement problems. It usually begins in childhood and leads to impaired muscle coordination (ataxia) that worsens over time. The disorder is named after Nicholaus Friedreich, a German doctor who first described the condition in the 1860s.

In Friedreichs ataxia the spinal cord and peripheral nerves degenerate, becoming thinner. The cerebellum, part of the brain that coordinates balance and movement, also degenerates to a lesser extent. This damage results in awkward, unsteady movements and impaired sensory functions. The disorder also causes problems in the heart and spine, and some people with the condition develop diabetes. The disorder does not affect thinking and reasoning abilities (cognitive functions).

Friedreichs ataxia is caused by a defect (mutation) in a gene labeled FXN. The disorder is recessive, meaning it occurs only in someone who inherits two defective copies of the gene, one from each parent. Although rare, Friedreichs ataxia is the most common form of hereditary ataxia, affecting about 1 in every 50,000 people in the United States. Both male and female children can inherit the disorder.

Symptoms typically begin between the ages of 5 and 15 years, although they sometimes appear in adulthood and on rare occasions as late as age 75. The first symptom to appear is usually gait ataxia, or difficulty walking. The ataxia gradually worsens and slowly spreads to the arms and the trunk. There is often loss of sensation in the extremities, which may spread to other parts of the body. Other features include loss of tendon reflexes, especially in the knees and ankles. Most people with Friedreich's ataxia develop scoliosis (a curving of the spine to one side), which often requires surgical intervention for treatment.

Dysarthria (slowness and slurring of speech) develops and can get progressively worse. Many individuals with later stages of Friedreichs ataxia develop hearing and vision loss.

Other symptoms that may occur include chest pain, shortness of breath, and heart palpitations. These symptoms are the result of various forms of heart disease that often accompany Friedreich's ataxia, such as hypertrophic cardiomyopathy (enlargement of the heart), myocardial fibrosis (formation of fiber-like material in the muscles of the heart), and cardiac failure. Heart rhythm abnormalities such as tachycardia (fast heart rate) and heart block (impaired conduction of cardiac impulses within the heart) are also common.

About 20 percent of people with Friedreich's ataxia develop carbohydrate intolerance and 10 percent develop diabetes. Most individuals with Friedreichs ataxia tire very easily and find that they require more rest and take a longer time to recover from common illnesses such as colds and flu.

The rate of progression varies from person to person. Generally, within 10 to 20 years after the appearance of the first symptoms, the person is confined to a wheelchair, and in later stages of the disease individuals may become completely incapacitated.

Friedreich's ataxia can shorten life expectancy, and heart disease is the most common cause of death. However, some people with less severe features of Friedreich's ataxia live into their sixties, seventies, or older.

A diagnosis of Friedreich's ataxia requires a careful clinical examination, which includes a medical history and a thorough physical exam, in particular looking for balance difficulty, loss of proprioception (joint sensation), absence of reflexes, and signs of neurological problems. Genetic testing now provides a conclusive diagnosis. Other tests that may aid in the diagnosis or management of the disorder include:

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Friedreich's Ataxia Fact Sheet: National Institute of ...

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Myelinated nerve fibers in the retina

Types: Usually recessive 1: INPP5E; 9q34 2: TMEM216; 11q12 3: AHI1; 6q23 4: NPHP1; 2q13 5: CEP290; 12q21 6: TMEM67; 8q22 7: RPGRIP1L; 16q12 8: ARL13B; 3q11 9: CC2D2A; 4p15 10: OFD1 (CXORF5); Xp22 11: TTC21B; 2q24; Dominant 12: KIF7; 15q26 13: TCTN1; 12q24 14: TMEM237; 2q33 15: CEP41; 7q32 15A: TCTN2; 12q24 16: TMEM138; 11q12 17: c5orf42; 5p13 18: TCTN3; 10q24 19: ZNF423; 16q12 20: TMEM231; 16q23 21: CSPP1; 8q13 22: PDE6D; 2q37 Joubert: EXOC8; 1q42 COACH syndromes CC2D2A; 4p15 TMEM67; 8q22 Nephronophthisis ATXN10; 22q13.31

Molar Tooth Sign

Metabolic ataxias

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Ataxia: Recessive - Neuromuscular Home Page

What is ataxia?

Ataxia describes the lack of muscle coordination when a voluntary movement is attempted. It may affect any motion that requires muscles to work together to perform a function, from walking to picking up an object to swallowing.

Ataxia is a sign of an underlying medical problem and is not a disease.

The cerebellum is the region of the brain that is responsible for coordinating motion in the body. When the brain commands part of the body to move, electrical signals are transmitted through the spinal cord into peripheral nerves that then stimulate a muscle to contract, initiating movement. That part of the body also has sensory nerves that collect information from the environment about position and proprioception, where the body is in time and space. These signals return via the same peripheral nerves but through a different pathway in the spinal cord. The cerebellum takes this information, as well as input from vision from the eyes and balance from the vestibular system of the inner ear, to help smooth out purposeful movement. Failure of any one or more of these pathway components can lead to ataxia.

Cerebellar ataxia is caused by abnormalities and damage, either temporary or permanent, to the cerebellum. Sensory ataxia occurs when the dorsal columns of the spinal cord fail to function normally. They are responsible for carrying proprioception information from the body to the brain. Damage to parts of the brain that have to interpret the information may also cause sensory ataxia. Vestibular ataxia describes loss of balance because the vestibular canals fail to function properly.

Ataxia maybe inherited and caused by a genetic defect or it may be acquired due to structural damage to the cerebellum or spinal cord.

Genetic ataxia may be sex linked, meaning that the DNA and gene problem is located on an X or Y chromosome (the sex chromosomes) or it may be autosomal linked, where the abnormality is located on one of the other 23 pairs of chromosomes.

Spinocerebellar and episodic ataxias are examples of autosomal dominant ataxias. Friedreich ataxia and ataxia telangiectasia are autosomal recessive.

Structural damage to the brain may be caused by any lesion that decreases blood supply to or invades into brain tissue, cerebellum included. This may include trauma and bleeding, stroke or tumor, and multiple sclerosis.

Poisonings, chemical, electrolyte, hormonal abnormalities, and malnutrition are also potential causes that tend to globally affect brain and body function and may or may not be reversible. Alcohol is perhaps the most common poisoning to cause ataxia. Other causes include a variety of prescription medications including lithium and those medications used to treat seizure disorders. Recreational drugs like PCP, ketamine, and marijuana may cause ataxia. Mercury poisoning may cause ataxia. Vitamin B12 deficiency and hypothyroidism are other potential causes.

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Ataxia: Get Facts on This Disorder - MedicineNet

Being diagnosed with Ataxia can be overwhelming. Below are a few frequently asked questions that can help you to understand ataxia better.

The word "ataxia", comes from the Greek word, " a taxis" meaning "without order or incoordination". The word ataxia means without coordination. People with ataxia have problems with coordination because parts of the nervous system that control movement and balance are affected. Ataxia may affect the fingers, hands, arms, legs, body, speech, and eye movements. The word ataxia is often used to describe a symptom of incoordination which can be associated with infections, injuries, other diseases, or degenerative changes in the central nervous system. Ataxia is also used to denote a group of specific degenerative diseases of the nervous system called the hereditary and sporadic ataxias which are the National Ataxia Foundation's primary emphases.

Diagnosis is based on a person's medical history, family history, and a complete neurological evaluation including an MRI scan of the brain. Various blood tests may be performed to rule out other possible disorders which may present similar symptoms. Genetic blood tests are now available for some types of hereditary ataxia to confirm a diagnosis or as a predictive test to determine if someone has inherited an ataxia gene known to affect other family members.

Symptoms and time of onset vary according to the type of ataxia. In fact there are often variations even within the same family with the same type of ataxia. Recessive disorders commonly cause symptoms to begin in childhood rather than adulthood. However, in recent years since genetic testing became available, it is now known the Friedreich's ataxia has an adult onset on some occasions. Dominant ataxia often begins in the 20s or 30s or even later in life. Sometimes individuals may not show symptoms until they are in their 60s.

Typically balance and coordination are affected first. In coordination of hands, arms, and legs, and slurring of speech are other common symptoms. Walking becomes difficult and is characterized by walking with feet placed further apart to compensate for poor balance. Impaired coordination of the arms and hands affect a person's ability to perform tasks requiring fine motor control such as writing and eating. Slow eye movements can be seen in some form of ataxia. As time goes on, ataxia can affect speech and swallowing.

The hereditary ataxias are degenerative disorders that progress over a number of years. How severe the disability will become and whether the disease will lead to death depends on type of ataxia, the age of onset of symptoms and other factors that are poorly understood at this time. Respiratory complications can be fatal in a person who is bed bound or who has severe swallowing problems. Some persons with Friedreich's ataxia develop serious cardiac problems.

There is a large group of people who have symptoms of ataxia that usually begin in adulthood and who have no known family history of this disease. This is called sporadic ataxia and it can be difficult to diagnose. There are many acquired and hereditary causes of ataxia which must be ruled out before a diagnosis of sporadic ataxia can be made. Sporadic ataxia can be either "pure cerebellar" if only the cerebellum is affected or cerebellar plus, if the ataxia is accompanied by additional symptoms such a neuropathy (dysfunction of the peripheral nerves); dementia (impaired intellectual function); or weakness, rigidity, or spasticity of the muscles. Disability may be greater and progress more quickly with the cerebellar plus form of sporadic ataxia. The cerebellar plus form of sporadic ataxia is also known as sporadic olivopontocerebellar ataxia ( sporadic OPCA) or multiple system atrophy, cerebellar type (MSA-C).

For people who have ataxia as a symptom of other medical conditions such as head injury, stroke, MS, alcoholism, etc., we recommend that you contact the organization related to your specific condition for the most up-to-date and accurate information.

The hereditary and sporadic ataxias are a complex group of diseases and this information is but a brief overview. You are welcome to download the ataxia information sheets from this website or contact the National Ataxia Foundation for additional information on hereditary and sporadic ataxias as well as more information on the genetics involved. This information is not intended in any way to replace information you have received from your doctor(s). Please note that we cannot answer specific questions concerning your situation, recommend drugs or suggest diagnosis. Please discuss these concerns with your doctor.

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National Ataxia Foundation - Diagnosis

Ataxia often occurs when parts of the nervous system that control movement are damaged. People with ataxia experience a failure of muscle control in their arms and legs, resulting in a lack of balance and coordination or a disturbance of gait. While the term ataxia is primarily used to describe this set of symptoms, it is sometimes also used to refer to a family of disorders. It is not, however, a specific diagnosis.

Most disorders that result in ataxia cause cells in the part of the brain called the cerebellum to degenerate, or atrophy. Sometimes the spine is also affected. The phrases cerebellar degeneration and spinocerebellar degeneration are used to describe changes that have taken place in a persons nervous system; neither term constitutes a specific diagnosis. Cerebellar and spinocerebellar degeneration have many different causes. The age of onset of the resulting ataxia varies depending on the underlying cause of the degeneration.

Many ataxias are hereditary and are classified by chromosomal location and pattern of inheritance: autosomal dominant, in which the affected person inherits a normal gene from one parent and a faulty gene from the other parent; and autosomal recessive, in which both parents pass on a copy of the faulty gene. Among the more common inherited ataxias are Friedreichs ataxia and Machado-Joseph disease. Sporadic ataxias can also occur in families with no prior history.

Ataxia can also be acquired. Conditions that can cause acquired ataxia include stroke, multiple sclerosis, tumors, alcoholism, peripheral neuropathy, metabolic disorders, and vitamin deficiencies.

There is no cure for the hereditary ataxias. If the ataxia is caused by another condition, that underlying condition is treated first. For example, ataxia caused by a metabolic disorder may be treated with medications and a controlled diet. Vitamin deficiency is treated with vitamin therapy. A variety of drugs may be used to either effectively prevent symptoms or reduce the frequency with which they occur. Physical therapy can strengthen muscles, while special devices or appliances can assist in walking and other activities of daily life.

The prognosis for individuals with ataxia and cerebellar/spinocerebellar degeneration varies depending on its underlying cause.

The NINDS supports and conducts a broad range of basic and clinical research on cerebellar and spinocerebellar degeneration, including work aimed at finding the cause(s) of ataxias and ways to treat, cure, and, ultimately, prevent them. Scientists are optimistic that understanding the genetics of these disorders may lead to breakthroughs in treatment.

Prepared by: Office of Communications and Public Liaison National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda, MD 20892

NINDS health-related material is provided for information purposes only and does not necessarily represent endorsement by or an official position of the National Institute of Neurological Disorders and Stroke or any other Federal agency. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient's medical history.

All NINDS-prepared information is in the public domain and may be freely copied. Credit to the NINDS or the NIH is appreciated.

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NINDS - Ataxia