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| + | DiseasesDB = 4980 | |
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| + | ICD10 = {{ICD10|G|11|1|g|10}} | |
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| + | ICD9 = {{ICD9|334.0}} | |
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| + | eMedicineSubj = neuro| |
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| + | eMedicineTopic = 139| |
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| + | '''Friedreich's ataxia''' is an [[inherited disease]] that causes [[Progressive illness|progressive damage]] to the [[nervous system]] resulting in symptoms ranging from [[gait disturbance]] and [[speech problem]]s to [[heart disease]]. |
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| − | + | Generally, [[ataxia]] is a symptom of [[coordination]] problems such as clumsy or awkward movements and unsteadiness and occurs in many different diseases and conditions. The ataxia of Friedreich's ataxia results from the [[degeneration]] of [[nerve 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 insular covering on some nerve cells that helps conduct [[nerve impulses]]). |
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| + | ==Eponym== |
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| ⚫ | |||
| + | The condition is named after the [[Germany|German]] physician [[Nikolaus Friedreich|Nicholaus Friedreich]], who first described it in the 1860s.<ref>{{WhoNamedIt|synd|1406}}</ref> |
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| + | ==Prevalence== |
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| − | Friedreich's ataxia is an [[autosome|autosomal]] [[recessive]] congenital ataxia and is caused by a [[mutation]] in [[Gene]] X25 that codes for [[frataxin]], located on [[chromosome]] 9. This protein is essential in neuronal and muscle cells for proper functioning mitochondria and the mutation causes inadequate production of frataxin. This results in, among other things, a degeneration of nerve tissue in the spinal cord. |
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| ⚫ | |||
| + | A 1984 Canadian study was able to trace 40 cases of classical Friedreich's disease from 14 [[French-Canadian]] kindreds previously thought to be unrelated to one common ancestral couple arriving in [[New France]] in 1634: [[Jean Guyon]] and Mathurine Robin.<ref>{{cite journal |author=Barbeau A, Sadibelouiz M, Roy M, Lemieux B, Bouchard JP, Geoffroy G |title=Origin of Friedreich's disease in Quebec |journal=The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques |volume=11 |issue=4 Suppl |pages=506–9 |year=1984 |pmid=6391645 |doi=}}</ref> |
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| ⚫ | |||
| + | About 20 percent of people with Friedreich's ataxia develop carbohydrate intolerance and 10 percent develop diabetes mellitus. |
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| ⚫ | Friedreich's ataxia and [[muscular dystrophy]], though often compared, are |
||
| + | ==Genetics== |
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| − | There are two types, the classic form and one in association with a genetic [[vitamin E]] deficiency. They cannot be distinguished clinically. |
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| + | |||
| + | [[Image:autorecessive.svg|thumb|right|{{PAGENAME}} has an autosomal recessive pattern of inheritance.]] |
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| + | |||
| + | Friedreich's ataxia is an [[autosome|autosomal]] [[recessive]] [[congenital]] ataxia and is caused by a [[mutation]] in [[gene]] FXN (formerly known as X25<ref>http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606829</ref>) that codes for [[frataxin]], located on [[chromosome]] 9. This protein is essential for proper functioning of [[mitochondria]] (it has been shown to be connected with the removal of iron from the [[cytoplasm]] surrounding the mitochondria, and in the absence of frataxin, the iron builds up and causes [[free radical]] damage). Nerve and [[muscle]] cells appear to be particularly sensitive to the deleterious effects of this type of mitochondrial dysfunction. |
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| + | |||
| + | The classic form of Friedreich's ataxia has been mapped to a gene on 9q13-q21 that affects production of the protein frataxin. In most cases, the mutant gene contains expanded [[Trinucleotide repeat disorders|GAA triplet repeats]] in the first [[intron]]; in a few pedigrees, [[point mutations]] have been detected. Because the defect is located on an intron (which is removed from the mRNA transcript between [[transcription]] and [[translation]]), this mutation does not result in the production of abnormal frataxin proteins. Instead, the mutation causes [[gene silencing]] (i.e., the mutation decreases the transcription of the gene) through induction of a [[heterochromatin]] structure in a manner similar to [[position-effect variegation]]. |
||
| + | |||
| + | ==Relationship to muscular dystrophy== |
||
| ⚫ | Friedreich's ataxia and the [[muscular dystrophy]] family of neuromuscular diseases, though often compared, are different diseases. Muscular dystrophies are the result of muscle tissue degeneration and [[atrophy]], whereas Friedreich's ataxia is the result of nerve degeneration caused by a [[Trinucleotide repeat disorders|trinucleotide repeat expansion]] mutation. Research on both disorders is supported by funding from the [[Muscular Dystrophy Association]]. |
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== Symptoms == |
== Symptoms == |
||
| − | Symptoms begin sometime between the ages of 5 to 15 years |
+ | 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: |
* Muscle weakness in the arms and legs |
* Muscle weakness in the arms and legs |
||
* Loss of coordination |
* Loss of coordination |
||
| − | * Vision impairment |
+ | * [[Visual perception|Vision]] impairment |
| − | * Hearing loss |
+ | * [[Hearing]] loss |
| − | * Slurred speech |
+ | * Slurred [[speech]] |
* Curvature of the spine ([[scoliosis]]) |
* Curvature of the spine ([[scoliosis]]) |
||
| + | * High [[plantar arch|plantar arches]] ( [[pes cavus]] deformity of the foot) |
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| − | * Carbohydrate intolerance |
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| + | * [[Diabetes]] |
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| − | * |
+ | * Heart disorders (e.g., [[atrial fibrillation]], and resultant [[tachycardia]] (fast heart rate) and hypertrophic [[cardiomyopathy]] ) |
| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
| + | These symptoms are slow and progressive. Long-term observation shows that many patients reach a plateau in symptoms in the patient's early adulthood. |
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| − | '''SIGNS''' |
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| + | ==Signs== |
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| − | nystagmus, fast saccadic eye movements, truncal titubation, dysarthria, dysmetria, absent deep tendon reflexes, extensor plantar responses, weakness which is greater distally are commonly found.loss of vibratory and proprioceptive sensation occurs. median age of death is 35 years, females have far better prognosis with 20year survival being 100% as compared to 63% in men. |
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| + | * [[Cerebellar]]: [[Nystagmus]], fast [[saccadic]] eye movements, truncal [[titubation]], [[dysarthria]], [[dysmetria]]. |
||
| − | cardiac involvment occurs in 90%of patients. cardiomegaly, symmetrical hypertrophy, murmurs, conduction defects. |
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| + | * [[Pyramidal]]: absent deep tendon reflexes, extensor plantar responses, and distal weakness are commonly found. |
||
| ⚫ | |||
| + | * [[Dorsal column]]: Loss of vibratory and proprioceptive sensation occurs. |
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| − | |||
| + | * Cardiac involvement occurs in 91% of patients, including [[cardiomegaly]] (up to dilated [[cardiomyopathy]]), symmetrical [[hypertrophy]], [[murmurs]], and conduction defects. Median age of death is 35 years, while females have better prognosis with a 20-year survival of 100% as compared to 63% in men.{{Fact|date=November 2007}} |
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| − | '''PATHOGENESIS''' |
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| ⚫ | |||
| − | primary site of pathology is spinal cord and peripheral nerves.sclerosis and degeneration of spinocerebellar tracts, lateral corticospinal tracts, and posterior columns. |
||
| − | in peripheral nerves there is a loss of large myelinated fibres. |
||
| + | ==Pathogenesis== |
||
| − | '''GENETICS''' |
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| + | The primary site of pathology is spinal cord and [[peripheral nerves]]. [[Sclerosis]] and [[degeneration]] of dorsal root ganglion, [[spinocerebellar tracts]], [[lateral]] [[corticospinal tract|corticospinal tracts]], and posterior columns<ref>{{cite journal |author=Delatycki M, Williamson R, Forrest S |title=Friedreich ataxia: an overview |journal=J Med Genet |volume=37 |issue=1 |pages=1–8 As |year=2000 |pmid=10633128 |doi=10.1136/jmg.37.1.1}}</ref>. In peripheral nerves there is a loss of large myelinated fibres. |
||
| − | Classic form has been mapped to 9q13-q21, and mutant gene contains expanded GAA triplet repeats in the first intron of "frataxin gene". |
||
== Treatment == |
== Treatment == |
||
| + | Currently, there is a treatment approved in Canada called [http://en.wikipedia.org/wiki/Catena_(idebenone) Catena (idebenone)] |
||
| + | . This prescription medicine is also under regulatory review in the European Union and Switzerland. In both the United States and in Europe there are two Phase III clinical trials on-going with [http://en.wikipedia.org/wiki/Catena_(idebenone) idebenone] |
||
| + | .<ref>http://www.clinicaltrials.gov/ct2/results?term=idebenone+friedreich%27s+idebenone</ref> |
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| ⚫ | A person suffering from Friedrich's Ataxia may require some surgical interventions (mainly for the spine and heart). Often a metal rod is inserted in the spine to help prevent or slow the progression of scoliosis. As progression of ataxia occurs, assistive devices such as a cane, walker, or wheelchair are required for mobility and independence. Other |
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| − | Up until recently, possibly due to a lack of understanding of what caused the lack of protein production, treatment has been focused on addressing the symptoms. On August 20th 2006, research findings circulated in Nature Chemical Biology which showed that compounds they developed could reactivate the defective gene in white blood cell samples and restore some level of the protein production. The scientists indicate if progress continues as expected, drugs for human sampling may be available around spring of 2008. |
||
| + | [[assistive technology]], such as a [[standing frame]], can help reduce the secondary complications of prolonged use of a [[wheelchair]]. |
||
| + | In many cases, patients experience significant heart conditions as well. These conditions, fortunately, are much more treatable, and are often countered with [[ACE inhibitor]]s such as enalapril or lisinopril and other heart medications such as [[digoxin]]. |
||
== See also == |
== See also == |
||
* [[Ataxia]] |
* [[Ataxia]] |
||
| + | |||
== External links == |
== External links == |
||
| − | *[http://www.ninds.nih.gov/disorders/friedreichs_ataxia/detail_friedreichs_ataxia.htm NIH Friedreich's Ataxia Fact Sheet] |
||
| ⚫ | |||
| ⚫ | |||
| − | *[http://www.mdausa.org/publications/Quest/q95friedreich.cfm Friedreich's Ataxia Enters 'the Treatment Era'] |
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| ⚫ | |||
| ⚫ | |||
| − | *[http://www.genetests.org/servlet/access?db=geneclinics&site=gt&id=8888892&key=RiUJpcnAjVaII&gry=&fcn=y&fw=FyvG&filename=/profiles/friedreich/index.html GeneReviews: Friedreich ataxia] |
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| + | *{{NINDS|friedreichs_ataxia}} |
||
| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
| ⚫ | |||
| + | * {{GeneTests|friedreich}} |
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| + | *[http://www.lacaf.org/index.php?option=com_frontpage&Itemid=1&lang=english Canadian Association for Familial Ataxias - Claude St-Jean Foundation] |
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| ⚫ | *Delatycki ''et al.'' (2000) provided an overview of the clinical features, [[pathology]], [[molecular genetics]], and possible therapeutic options in Friedreich's ataxia.<ref>{{cite journal |author=Delatycki M, Williamson R, Forrest S |title=Friedreich ataxia: an overview |journal=J Med Genet |volume=37 |issue=1 |pages=1–8 As |year=2000 |pmid=10633128 |doi=10.1136/jmg.37.1.1}}</ref> |
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| + | * [http://www.bcataxia.org/ British Columbia (BC) Ataxia Society ] |
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| + | |||
| + | ==References== |
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| + | {{Reflist}} |
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| + | |||
| + | {{Diseases of the nervous system}} |
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| + | {{Mitochondrial diseases}} |
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| + | {{Trinucleotide repeat disorders}} |
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| + | |||
| + | [[Category:Neurological disorders]] |
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| ⚫ | |||
| + | [[Category:Autosomal recessive disorders]] |
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| + | [[Category:Mitochondrial diseases]] |
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| + | <!-- |
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| + | [[ca:Atàxia de Friedreich]] |
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[[de:Friedreich-Ataxie]] |
[[de:Friedreich-Ataxie]] |
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[[es:Ataxia de Friedreich]] |
[[es:Ataxia de Friedreich]] |
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| + | [[fa:آتاکسی فردریش]] |
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[[fr:Ataxie de Friedreich]] |
[[fr:Ataxie de Friedreich]] |
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| + | [[it:Atassia di Friedreich]] |
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[[he:אטקסיית פרידרייך]] |
[[he:אטקסיית פרידרייך]] |
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| − | [[hu:Friedreich |
+ | [[hu:Friedreich-ataxia]] |
| + | [[nl:Ataxie van Friedreich]] |
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[[pl:Choroba Friedreicha]] |
[[pl:Choroba Friedreicha]] |
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| + | [[ru:Атаксия Фридрейха]] |
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| + | --> |
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{{enWP|Friedreich's ataxia}} |
{{enWP|Friedreich's ataxia}} |
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Latest revision as of 00:51, 7 March 2009
Assessment |
Biopsychology |
Comparative |
Cognitive |
Developmental |
Language |
Individual differences |
Personality |
Philosophy |
Social |
Methods |
Statistics |
Clinical |
Educational |
Industrial |
Professional items |
World psychology |
Clinical: Approaches · Group therapy · Techniques · Types of problem · Areas of specialism · Taxonomies · Therapeutic issues · Modes of delivery · Model translation project · Personal experiences ·
| ICD-10 | G111 | |
|---|---|---|
| ICD-9 | 334.0 | |
| OMIM | 229300 | |
| DiseasesDB | 4980 | |
| MedlinePlus | [1] | |
| eMedicine | neuro/139 | |
| MeSH | {{{MeshNumber}}} | |
Friedreich's ataxia is an inherited disease that causes progressive damage to the nervous system resulting in symptoms ranging from gait disturbance and speech problems to heart disease.
Generally, ataxia is a symptom of coordination problems such as clumsy or awkward movements and unsteadiness and occurs in many different diseases and conditions. The ataxia of Friedreich's ataxia results from the degeneration of nerve 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 insular covering on some nerve cells that helps conduct nerve impulses).
Eponym
The condition is named after the German physician Nicholaus Friedreich, who first described it in the 1860s.[1]
Prevalence
Friedreich's ataxia is the most prevalent inherited ataxia, affecting about 1 in 50,000 people in the United States. Males and females are affected equally. The estimated carrier prevalence is 1:110.
A 1984 Canadian study was able to trace 40 cases of classical Friedreich's disease from 14 French-Canadian kindreds previously thought to be unrelated to one common ancestral couple arriving in New France in 1634: Jean Guyon and Mathurine Robin.[2]
About 20 percent of people with Friedreich's ataxia develop carbohydrate intolerance and 10 percent develop diabetes mellitus.
Genetics
Friedreich's ataxia has an autosomal recessive pattern of inheritance.
Friedreich's ataxia is an autosomal recessive congenital ataxia and is caused by a mutation in gene FXN (formerly known as X25[3]) that codes for frataxin, located on chromosome 9. This protein is essential for proper functioning of mitochondria (it has been shown to be connected with the removal of iron from the cytoplasm surrounding the mitochondria, and in the absence of frataxin, the iron builds up and causes free radical damage). Nerve and muscle cells appear to be particularly sensitive to the deleterious effects of this type of mitochondrial dysfunction.
The classic form of Friedreich's ataxia has been mapped to a gene on 9q13-q21 that affects production of the protein frataxin. In most cases, the mutant gene contains expanded GAA triplet repeats in the first intron; in a few pedigrees, point mutations have been detected. Because the defect is located on an intron (which is removed from the mRNA transcript between transcription and translation), this mutation does not result in the production of abnormal frataxin proteins. Instead, the mutation causes gene silencing (i.e., the mutation decreases the transcription of the gene) through induction of a heterochromatin structure in a manner similar to position-effect variegation.
Relationship to muscular dystrophy
Friedreich's ataxia and the muscular dystrophy family of neuromuscular diseases, though often compared, are different diseases. Muscular dystrophies are the result of muscle tissue degeneration and atrophy, whereas Friedreich's ataxia is the result of nerve degeneration caused by a trinucleotide repeat expansion mutation. Research on both disorders is supported by funding from the Muscular Dystrophy Association.
Symptoms
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:
- Muscle weakness in the arms and legs
- Loss of coordination
- Vision impairment
- Hearing loss
- Slurred speech
- Curvature of the spine (scoliosis)
- High plantar arches ( pes cavus deformity of the foot)
- Diabetes
- Heart disorders (e.g., atrial fibrillation, and resultant tachycardia (fast heart rate) and hypertrophic cardiomyopathy )
It presents before 25 years of age with progressive staggering or stumbling gait and frequent falling. Lower extremities are more severely involved.
These symptoms are slow and progressive. Long-term observation shows that many patients reach a plateau in symptoms in the patient's early adulthood.
Signs
- Cerebellar: Nystagmus, fast saccadic eye movements, truncal titubation, dysarthria, dysmetria.
- Pyramidal: absent deep tendon reflexes, extensor plantar responses, and distal weakness are commonly found.
- Dorsal column: Loss of vibratory and proprioceptive sensation occurs.
- Cardiac involvement occurs in 91% of patients, including cardiomegaly (up to dilated cardiomyopathy), symmetrical hypertrophy, murmurs, and conduction defects. Median age of death is 35 years, while females have better prognosis with a 20-year survival of 100% as compared to 63% in men.[How to reference and link to summary or text]
20% of cases are found in association with diabetes mellitus type 1 or 2 or pancreatic β cell dysfunction.
Pathogenesis
The primary site of pathology is spinal cord and peripheral nerves. Sclerosis and degeneration of dorsal root ganglion, spinocerebellar tracts, lateral corticospinal tracts, and posterior columns[4]. In peripheral nerves there is a loss of large myelinated fibres.
Treatment
Currently, there is a treatment approved in Canada called Catena (idebenone) . This prescription medicine is also under regulatory review in the European Union and Switzerland. In both the United States and in Europe there are two Phase III clinical trials on-going with idebenone .[5]
A person suffering from Friedrich's Ataxia may require some surgical interventions (mainly for the spine and heart). Often a metal rod is inserted in the spine to help prevent or slow the progression of scoliosis. As progression of ataxia occurs, assistive devices such as a cane, walker, or wheelchair are required for mobility and independence. Other assistive technology, such as a standing frame, can help reduce the secondary complications of prolonged use of a wheelchair.
In many cases, patients experience significant heart conditions as well. These conditions, fortunately, are much more treatable, and are often countered with ACE inhibitors such as enalapril or lisinopril and other heart medications such as digoxin.
See also
External links
- FARA What is Friedreich's Ataxia? at www.cureFA.org
- Asks the Experts - Responses: Friedreich's Ataxia at Muscular Dystrophy Association
- NCBI Genes and Disease: Friedreich's ataxia at National Center for Biotechnology Information
- GeneTests at NIH/UW friedreich
- Canadian Association for Familial Ataxias - Claude St-Jean Foundation
- Delatycki et al. (2000) provided an overview of the clinical features, pathology, molecular genetics, and possible therapeutic options in Friedreich's ataxia.[6]
- British Columbia (BC) Ataxia Society
References
- ↑ Who Named It synd/1406
- ↑ Barbeau A, Sadibelouiz M, Roy M, Lemieux B, Bouchard JP, Geoffroy G (1984). Origin of Friedreich's disease in Quebec. The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques 11 (4 Suppl): 506–9.
- ↑ http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606829
- ↑ Delatycki M, Williamson R, Forrest S (2000). Friedreich ataxia: an overview. J Med Genet 37 (1): 1–8 As.
- ↑ http://www.clinicaltrials.gov/ct2/results?term=idebenone+friedreich%27s+idebenone
- ↑ Delatycki M, Williamson R, Forrest S (2000). Friedreich ataxia: an overview. J Med Genet 37 (1): 1–8 As.
Template:Mitochondrial diseases Template:Trinucleotide repeat disorders
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