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| {{Infobox_Disease | | | {{Friedreich's ataxia}} |
| Name = {{PAGENAME}} |
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| Image = |
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| Caption = |
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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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| ICDO = |
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| OMIM = 229300 |
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| MedlinePlus = |
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| MeshID = D005621 |
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| }}
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| {{SI}}
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| {{CMG}}, {{AE}}{{MMJ}}
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| ==Historical Perspective==
| | {{CMG}}, {{AE}} {{sali}}, [[User:M Jahan|Mohamadmostafa Jahansouz M.D]], {{M.B}} |
| ===Discovery===
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| *Friedreich’s ataxia was first discovered by Nikolaus Friedreich, a German [[pathologist]] and [[neurologist]], in 1863.
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| *The association between hereditary inheritance and Friedreich’s ataxia was made first time by Nikolaus Friedreich.
| | ==[[Friedreich's ataxia overview|Overview]]== |
| *In 1996, the association between a GAA repeat expansion on [[chromosome 9]] and the development of Friedreich's ataxia was discovered for the first time.
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| ===Famous Cases===
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| *Geraint Williams: He is known for scaling Mount Kilimanjaro in an adaptive wheelchair known as a Mountain Trike.
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| ==Classification== | | ==[[Friedreich's ataxia historical perspective|Historical Perspective]]== |
| There is no established system for the classification of Friedreich's ataxia.
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| == Pathophysiology == | | ==[[Friedreich's ataxia classification|Classification]]== |
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| === Pathogenesis and genetics === | | ==[[Friedreich's ataxia pathophysiology|Pathophysiology]]== |
| * It is understood that Friedreich’s ataxia is the result of a [[homozygous]] [[guanine]]-[[adenine]]-[[adenine]] (GAA) [[Trinucleotide repeat expansion disorders|trinucleotide repeat expansion]] on chromosome 9q13 that causes a transcriptional defect of the [[frataxin]] gene.
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| * [[Frataxin]] is a small mitochondrial protein and deficiency of [[frataxin]] is responsible for all clinical and morphological manifestations of Friedreich’s ataxia.
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| * The severity of the disease is directly related to the length of the [[Trinucleotide repeat expansion disorders|trinucleotide repeat expansion]] and long expansions lead to early onset, severe clinical illness, and death in young adult life.
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| * Patients with short [[Trinucleotide repeat expansion disorders|trinucleotide repeat expansion]] have a later onset and a more benign course and even some of them are not diagnosed during life.
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| * Friedreich’s ataxia is transmitted in [[Autosomal recessive disorder|autosomal recessive]] pattern.
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| * Because the frataxin protein has multiple functions in the normal state, the exact role of frataxin deficiency in the pathogenesis of Friedreich's ataxia is still unclear. These functions include:
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| ** Biogenesis of [[Iron-sulfur cluster|iron-sulfur clusters]]
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| ** Iron chaperoning
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| ** Iron storage
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| ** Control of iron-mediated oxidative tissue damage
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| *
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| == Associated Conditions == | | ==[[Friedreich's ataxia causes|Causes]]== |
| Conditions associated with friedreich’s ataxia include:
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| * Hypertrophic cardiomyopathy
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| * [[Diabetes mellitus]]
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| * [[Scoliosis]]
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| * Distal wasting
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| * [[Optic atrophy]]
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| * [[Sensorineural deafness]]
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| * [[Sleep apnea]]
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| *[[Pes cavus]] in 55% to 75% of cases
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| == Gross Pathology == | | ==[[Friedreich's ataxia differential diagnosis|Differentiating Any Disease from other Diseases]]== |
| On gross pathology involvement of spinal cord, [[cerebellum]], and heart are characteristic findings of Friedreich's ataxia.
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| '''Spinal cord''' lesions include:
| | ==[[Friedreich's ataxia epidemiology and demographics|Epidemiology and Demographics]]== |
| *Decreased transverse diameter of the [[spinal cord]] at all levels
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| **The thinning is especially evident in the thoracic region
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| *Thin and gray dorsal spinal roots
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| *Smallness and gray discoloration of the [[dorsal column]]
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| *Thin and gray [[gracile]] and [[Cuneate fasciculus|cuneate fasciculi]]
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| *Fiber loss in the anterolateral fields corresponding to [[Spinocerebellar tract|spinocerebellar]] and [[Corticospinal tract|corticospinal tracts]]
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| '''Cerebellum''' lesions include:
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| *Atrophy of the [[Dentate nucleus|dentate nuclei]] and its efferent fibers
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| '''Heart''' findings include:
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| * Increased heart weight
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| * Increased thickness of left and right ventricular walls and [[interventricular septum]]
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| * Dilatation of the [[ventricles]]
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| * “Marble”-like discoloration of the [[myocardium]]
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| == Microscopic Pathology == | | ==[[Friedreich's ataxia risk factors|Risk Factors]]== |
| On microscopic histopathological analysis, involvement of [[spinal cord]], [[cerebellum]], [[heart]] and [[pancreas]] are characteristic findings of Friedreich's ataxia.
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| '''<big>Spinal cord</big>''' | | ==[[Friedreich's ataxia screening|Screening]]== |
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| *Friedreich’s ataxia mostly affects the [[dorsal root ganglia]] (DRG) of the spinal cord. It affects the entire DGR but is most prominent in subcapsular regions.
| | ==[[Friedreich's ataxia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| *Cell stains in samples of DGN reveal:<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
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| **An overall reduction in the size of [[ganglion cells]]
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| **The absence of very large [[Neuron|neurons]] and large [[Myelinated|myelinated fibers]]
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| **Clusters of nuclei representing “residual nodules” that indicate an invasion-like entry of [[Satellite cells|satellite]] cells into the [[cytoplasm]] of neurons.
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| **Progressive destruction of neuronal cytoplasm in cytoskeletal stains, such as for class-III-β-tubulin
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| **Greatly thickened [[satellite cells]]
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| **Residual nodules remain strongly reactive with anti-S100α in the satellite cells
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| **Increased [[ferritin]] immunoreactivity in satellite cells
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| '''<big>Cerebellum</big>'''
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| * Friedreich’s ataxia mostly affects the [[dentate nucleus]] of [[cerebellum]]<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
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| * Cell stains in samples of [[cerebellum]] reveal:<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
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| ** The absence of very large [[Neuron|neurons]]
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| ** Severe loss of [[γ-aminobutyric acid]] (GABA)-containing terminals in the immunostaining with an antibody to [[glutamic acid decarboxylase]] (GAD)
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| ** Grumose degeneration in the immunostaining with anti-GAD
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| ** Punctate reaction product in areas known to be rich in [[Mitochondrion|mitochondria]], namely, neuronal cytoplasm and synaptic terminals
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| ** [[Frataxin]]-deficient [[mitochondria]]
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| '''<big>Heart</big>'''
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| * Cell stains in samples of heart reveal:<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
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| ** Collections of tiny reactive inclusions in a small percentage of [[Cardiomyocyte|cardiomyocytes]] that are arranged in parallel with [[myofibrils]] in the iron stains
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| ** Electron-dense inclusions in [[Mitochondrion|mitochondria]]
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| ** [[Myocardial]] fiber necrosis and an inflammatory reaction in the severe cases of [[cardiomyopathy]]
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| '''<big>Pancreas</big>'''
| | ==Diagnosis== |
| * Cell stains in samples of [[pancreas]] reveal:<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
| | [[Friedreich's ataxia history and symptoms|History and Symptoms]] | [[Friedreich's ataxia physical examination|Physical Examination]] | [[Friedreich's ataxia laboratory findings|Laboratory Findings]] | [[Friedreich's ataxia electrocardiogram|Electrocardiogram]] | [[Friedreich's ataxia chest x ray|Chest X Ray]] | [[Friedreich's ataxia CT|CT]] | [[Friedreich's ataxia MRI|MRI]] | [[Friedreich's ataxia echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Friedreich's ataxia other imaging findings|Other Imaging Findings]] | [[Friedreich's ataxia other diagnostic studies|Other Diagnostic Studies]] |
| ** Lose of the sharp demarcation of the [[synaptophysin]]-positive [[Islets of Langerhans|islets]] of [[pancreas]]
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| ** The “fade” appearance of the β-cells into the surrounding exocrine [[pancreas]]
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| == Causes == | | ==Treatment== |
| === Genetic Causes ===
| | [[Friedreich's ataxia medical therapy|Medical Therapy]] | [[Friedreich's ataxia surgery|Surgery]] | [[Friedreich's ataxia primary prevention|Primary Prevention]] | [[Friedreich's ataxia secondary prevention|Secondary Prevention]] | [[Friedreich's ataxia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Friedreich's ataxia future or investigational therapies|Future or Investigational Therapies]] |
| * It is understood that Friedreich’s ataxia is the result of a [[homozygous]] [[guanine]]-[[adenine]]-[[adenine]] (GAA) [[Trinucleotide repeat expansion disorders|trinucleotide repeat expansion]] on chromosome 9q13 that causes a transcriptional defect of the [[frataxin]] gene.<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
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| * [[Frataxin]] is a small mitochondrial protein and deficiency of [[frataxin]] is responsible for all clinical and morphological manifestations of Friedreich’s ataxia.<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
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| ==Differentiating Friedreich’s ataxia from other Diseases== | | ==Case Studies== |
| As Friedreich’s ataxia manifests in a variety of clinical forms and different ages, differentiation must be established in accordance with the manifestations of the disease and onset of the symptoms.
| | [[Category:Projects]] |
| | [[Category:Help]] |
| | [[Friedreich's ataxia here case study one|Case #1]] |
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| The main and most prominent symptom of the Friedreich’s ataxia is [[ataxia]] that worsens over time and it must be differentiated from other diseases that cause progressive [[ataxia]] such as:
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| * [[Spinocerebellar ataxia|Spinocerebellar ataxias (SCA)]]
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| * [[Dentatorubral-pallidoluysian atrophy|Dentato-rubro-pallido-luysian atrophy]]
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| * [[Episodic ataxia]]
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| * [[Spastic ataxia]]
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| * [[Abetalipoproteinemia]]
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| * [[Refsum's disease|Refsum disease]]
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| * Hypomyelinating leukoencephalopathy: Hypomyelination, [[basal ganglia]] atrophy, rigidity, [[dystonia]], [[chorea]]
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| * Pure cerebellar ataxia: Other family members of these patients may have [[frontotemporal dementia]] or motor neuron disease
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| * Progressive cerebellar [[atrophy]] with epileptic [[encephalopathy]]: Infantile [[seizures]], intellectual deficits, [[microcephaly]]
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| * Rapid-onset ataxia: Cerebellar atrophy
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| * CAPOS mutation: ([[Cerebellar ataxia]], [[areflexia]], [[Pes cavus]], [[optic atrophy]], [[sensorineural hearing loss]], and [[Alternating hemiplegia|alternating hemiplegia)]]
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| == Epidemiology and Demographics ==
| | {{Infobox_Disease | |
| | | Name = {{PAGENAME}} | |
| === Incidence ===
| | Image = | |
| * The incidence of Friedreich’s ataxia is approximately 2-4 per 100,000 individuals worldwide.
| | Caption = | |
| | | DiseasesDB = 4980 | |
| === Prevalence ===
| | ICD10 = {{ICD10|G|11|1|g|10}} | |
| * The prevalence of Friedreich’s ataxia is approximately 2-4 per 100,000 individuals worldwide.
| | ICD9 = {{ICD9|334.0}} | |
| | | ICDO = | |
| === Age ===
| | OMIM = 229300 | |
| * Friedreich ataxia commonly affects individuals from early childhood through to early adulthood, starting with poor balance when walking, followed by slurred speech and upper-limb ataxia.<ref name="pmid20301458">{{cite journal |vauthors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Bidichandani SI, Delatycki MB |title= |journal= |volume= |issue= |pages= |date= |pmid=20301458 |doi= |url=}}</ref>
| | MedlinePlus = | |
| * Friedreich ataxia is usually first diagnosed at age 10 to 15 years but onset of disease may be as early as age 2 years and as late as the 8th decade.<ref name="pmid20301458">{{cite journal |vauthors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Bidichandani SI, Delatycki MB |title= |journal= |volume= |issue= |pages= |date= |pmid=20301458 |doi= |url=}}</ref>
| | MeshID = D005621 | |
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| === Race and Region ===
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| *The GAA triplet repeat expansion that causes Friedreich ataxia usually affects only individuals of the European, North African, Middle Eastern, or Indian origin (Indo-European and Afro-Asiatic speakers).
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| *Sub-Saharan Africans, Amerindians, and individuals from China, Japan, and Southeast Asia are less likely to develop Friedreich ataxia.<ref name="pmid10881262">{{cite journal |vauthors=Labuda M, Labuda D, Miranda C, Poirier J, Soong BW, Barucha NE, Pandolfo M |title=Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion |journal=Neurology |volume=54 |issue=12 |pages=2322–4 |date=June 2000 |pmid=10881262 |doi= |url=}}</ref>
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| === Gender ===
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| * Friedreich ataxia affects men and women equally.<ref name="pmid3062632">{{cite journal |vauthors=Marcus AJ, Safier LB, Ullman HL, Islam N, Broekman MJ, Falck JR, Fischer S, von Schacky C |title=Cell-cell interactions in the eicosanoid pathways |journal=Prog. Clin. Biol. Res. |volume=283 |issue= |pages=559–67 |date=1988 |pmid=3062632 |doi= |url=}}</ref>
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| * Female are more commonly affected by clinical fractures than male.<ref name="pmid20301458">{{cite journal |vauthors=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, Bidichandani SI, Delatycki MB |title= |journal= |volume= |issue= |pages= |date= |pmid=20301458 |doi= |url=}}</ref>
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| ==Eponymjhjmfkkdiemmdkmvwkxmlkmwojdndkwqmas,ls,sckdlcm,sapl,as;ldpsclcmdl,a;,vndkm==
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| It is named after the German physician [[Nikolaus Friedreich|Nicholaus Friedreich]], who first described the condition in the 1860s.
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| ==Prevalence==
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| Friedreich's ataxia, although rare, is the most prevalent inherited ataxia, affecting about 1 in 50,000 people in the United States. Males and females are affected equally.
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| Due to the relatively heterogenous population of Quebec, a 1984 Canadian study was able to trace 40 cases of classical Friedreich's disease from 14 previously unrelated French-Canadian kindreds to one common ancestral couple arriving in New France in 1634: Jean Guyon and Mathurine Robin.
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| Delatycki et al. (2000) provided an overview of the clinical features, [[pathology]], molecular genetics, and possible therapeutic options in Friedreich ataxia.
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| ==Genetics== | |
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| Friedreich's ataxia is an [[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 (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).
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| The classic form has been mapped to 9q13-q21; the mutant gene contains expanded GAA triplet repeats in the first intron of "frataxin gene". 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 (the mutation decreases the transcription of the gene) through induction of a heterochromatin structure in a manner similar to position-effect variegation.
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| ==Relationship to muscular dystrophy==
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| Friedreich's ataxia and [[muscular dystrophy]], though often compared, are completely different diseases. Muscular dystrophy is the result of muscle tissue degeneration whereas Friedreich's ataxia is the result of nerve tissue degeneration caused by a [[Trinucleotide repeat disorders|trinucleotide repeat expansion]] mutation. Both are researched by the [[Muscular Dystrophy Association]].
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| ==Types of Friedreich's ataxia==
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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 in lab.
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| == Symptoms ==
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| Symptoms typically begin sometime between the ages of 5 to 15 years, but in Late Onset FA may occur in the 20's or 30's. Symptoms include any combination, but not necessarily all of the following:
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| * Muscle weakness in the arms and legs
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| * Loss of coordination
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| * Vision impairment
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| * Hearing loss
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| * Slurred speech
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| * Curvature of the spine ([[scoliosis]])
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| * High plantar arches
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| * Diabetes
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| * Extreme heart conditions (e.g., [[atrial fibrillation]], and resultant [[tachycardia]] (fast heart rate) and [[cardiomyopathy]] (enlargement of the heart))
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| It presents before 25 years of age with progressive staggering gait, frequent falling and titubation. Lower extremities are more severely involved.
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| These symptoms are slow and progressive. Long-term observation shows that many patients reach a plateau in symptoms in the patient's early adulthood. Because of many of these symptoms, 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 occurs, assistive devices such as a cane or walker or a wheelchair are required for mobility (independence).
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| ==Signs==
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| * [[Cerebellar]]: [[Nystagmus]], fast saccadic eye movements, truncal titubation, [[dysarthria]], [[dysmetria]].
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| * Pyramidal: absent deep tendon reflexes, extensor plantar responses, and distal weakness are commonly found.
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| * [[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.
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| 20% cases are found in association with diabetes mellitus type 1 or 2 or pancreatic β cell dysfunction.
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| ==Diagnosis==
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| *Cardiac MRI is indicated in patients suspected of this disease.
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| ===AHA Scientific Statement: Management of Cardiac Involvement Associated With Neuromuscular Diseases===
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| ====Cardiac Evaluation in Friedrich Ataxia (FA)====
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| {| class="wikitable" style="width:80%"
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| | colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
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| |-
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| | bgcolor="LightGreen" |<nowiki>"</nowiki>'''1.''' Cardiology evaluation with examination, ECG, echocardiogram, and ambulatory electrocardiographic monitoring should occur at the time of FA diagnosis. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
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| |-
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| | bgcolor="LightGreen" |<nowiki>"</nowiki>'''2.''' Asymptomatic FA patients should be followed up at least annually with examination, ECG, and echocardiogram. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
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| |-
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| | bgcolor="LightGreen" |<nowiki>"</nowiki>'''3.''' Symptomatic FA patients should be followed up more frequently than annually. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
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| | colspan="1" style="text-align:center; background:LemonChiffon" | [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
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| | bgcolor="LemonChiffon" |<nowiki>"</nowiki>'''1.''' Ambulatory electrocardiographic monitor- ing or monitoring with an event recorder is reasonable in FA patients with symptoms of palpitations and in those without symptoms every 1 to 4 years, increasing in frequency with increasing age. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])'' <nowiki>"</nowiki>
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| |}
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| ===ACC/AHA Guidelines- ACCF/ACR/AHA/NASCI/SCMR 2010 Expert Consensus Document on Cardiovascular Magnetic Resonance (DO NOT EDIT)===
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| {{cquote|
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| CMR may be used for assessment of patients with LV dysfunction or hypertrophy or suspected forms of cardiac injury not related to
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| ischemic heart disease. When the diagnosis is unclear, CMR may be considered to identify the etiology of cardiac dysfunction in
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| patients presenting with heart failure, including
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| *evaluation of dilated cardiomyopathy in the setting of normal coronary arteries,
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| *patients with positive cardiac enzymes without obstructive atherosclerosis on angiography,
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| *patients suspected of amyloidosis or other infiltrative diseases,
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| *hypertrophic cardiomyopathy,
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| *arrhythmogenic right ventricular dysplasia, or
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| *syncope or ventricular arrhythmia.
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| }} | | }} |
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| ==Pathogenesis==
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| The 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.
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| == Treatment ==
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| The symptoms can be treated but there is no treatment for Friedrich's Ataxia at this time. There are several clinical trials taking place, including one for idebenone, in the United States. [[Assistive Technology]], such as a [[standing frame]], can help reduce the secondary complications of prolonged use of a [[wheelchair]].
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| 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 Lisinopril and other heart medications such as Digoxin.
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| ==Current Research==
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| Recent research led by Joel Gottesfeld of The Scripps Research Institute has indicated that Histone Deacetylase Inhibitors are able to reverse the silencing of the frataxin gene in human primary lymphocytes. This class of chemicals is thought to enable DNA transcription of the frataxin gene because the inhibition of histone deacetylation, makes the terminal tails of histones H3 and H4 more likely to remain fully acetylated. Acetylation removes the positive charge from the lysine (an amino acid that is a part of the n-terminal tail of the histone proteins), and thus makes the histones less able to neutralize the charges of the DNA (specifically the negatively charged phosphate backbone). This causes the DNA and the histone proteins to be less condensed (back to the form of euchromatin). This increases the ability of regulatory proteins and RNA polymerases to access the frataxin gene, and therefore returns the transcription (and the overall expression) of the frataxin gene to normal levels.
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| Because the genetic defect occurs in the intron, the excess nucleotides repeats are removed from the mRNA transcript, and the resulting frataxin proteins are not defective. The HDACi chemicals effect the histone proteins throughout the cell, but gene expression microarray experiments reveal that the effects are limited, and do not appear to be clustered into any family of genes that might cause deleterious side effects. The compounds are not cytotoxic to lymphocytes or to mice when administered at therapeutic doses.
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| On April 11th, 2007, Repligen Corporation, a biopharmaceutical company, entered into an exclusive commercial license with The Scripps Research Institute for the development of HDACi compounds that could have clinical uses in the treatment of Friedreich's Ataxia.
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| == See also ==
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| * [[Ataxia]]
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| ==References==
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| <references />
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| == External links ==
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| '''Friedreich's Ataxia Research Alliance (FARA)''' http://www.cureFA.org
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| '''Patient Recruitment for Friedreich's Ataxia Upcoming Clinical Research Trials:''' to sign up
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| http://www.cureFA.org/registry/
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| '''FARA Electronic News Bulletin''' for latest research and news relevant to Friedreich's ataxia: To sign up
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| http://visitor.constantcontact.com/email.jsp?m=1101190303489
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| *[http://www.cureFA.org/education/friedreichs_ataxia.asp FARA What is Friedreich's Ataxia?] at www.cureFA.org
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| *[http://health.groups.yahoo.com/group/FA_BabelFAmily/ Babel FAmily] Multilingual mailing-list about Friedreich's ataxia. Includes latest news about research and fundraising to help defeat this neurodegenerative disease. at [[Yahoo! Groups]]
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| *{{NINDS|friedreichs_ataxia}}
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| *[http://www.mdausa.org/experts/responses.cfm?id=92 Asks the Experts - Responses: Friedreich's Ataxia] at [[Muscular Dystrophy Association]]
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| *[http://www.mdausa.org/publications/Quest/q95friedreich.cfm Friedreich's Ataxia Enters 'the Treatment Era'] at [[Muscular Dystrophy Association]]
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| *[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.205 NCBI Genes and Disease: Friedreich's ataxia] at [[National Center for Biotechnology Information]]
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| * {{GeneTests|friedreich}}
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| *[http://www.ataxiaforums.co.uk Ataxia Forums] at ataxiaforums.co.uk
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| * [http://www.mdahellas.gr/ Muscular Dystrophy Association's website in Greece] at mdahellas.gr
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| * http://www.curefa.org/news/pr_2007-04-11.asp
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| * http://www.lacaf.org/en/ Canadian Association for Familial Ataxias - Claude St-Jean Foundation
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| {{Diseases of the nervous system}}
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| {{Mitochondrial diseases}}
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| [[Category:Neurological disorders]] | | [[Category:Neurological disorders]] |
| [[Category:Genetic disorders]] | | [[Category:Genetic disorders]] |
| [[Category:Mitochondrial diseases]] | | [[Category:Mitochondrial diseases]] |
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| [[ca:Atàxia de Friedreich]]
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| [[de:Friedreich-Ataxie]]
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| [[es:Ataxia de Friedreich]] | | [[es:Ataxia de Friedreich]] |
| [[fr:Ataxie de Friedreich]] | | [[fr:Ataxie de Friedreich]] |
| [[he:אטקסיית פרידרייך]]
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| [[hu:Friedreich ataxia]]
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| [[pl:Choroba Friedreicha]] | | [[pl:Choroba Friedreicha]] |
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