请输入您要查询的百科知识：

　

词条 Friedreich's ataxia
释义

  1. Signs and symptoms

  2. Causes

  3. Pathophysiology

  4. Diagnosis and monitoring

  5. Management

     Rehabilitation  Speech therapy  Devices  Medication  Surgery 

  6. Prognosis

  7. Epidemiology

     Haplogroup R1b 

  8. History

  9. Research

     Discontinued efforts 

  10. Society and culture

  11. External links

  12. References

{{short description|Rare autosomal recessive human disease}}{{Use American English|date=March 2019}}{{Infobox medical condition (new)
| synonyms = Spinocerebellar ataxia, FRDA, FA
| name = Friedreich's ataxia
| image = Protein FXN PDB 1ekg.png
| caption = Frataxin
| pronounce =
| field = Neurology
| symptoms = Lack of coordination, balance issues, gait abnormality
| complications = Cardiomyopathy, scoliosis, diabetes mellitus
| onset = 5–15 years
| duration = Long-term
| types =
| causes = Genetic
| risks =
| diagnosis = Investigation of the medical history and a thorough physical examination
| differential =
| prevention =
| treatment = Physical therapy
| medication =
| prognosis =
| frequency = 1 in 50,000 in the United States
| deaths =
|alt=}}

Friedreich's ataxia (FRDA, or FA) is an autosomal recessive genetic disease that causes difficulty walking, a loss of sensation in the arms and legs and impaired speech that worsens over time. Many patients have a form of heart disease called hypertrophic cardiomyopathy. Symptoms typically start between the ages of 5 and 15 years, although they may present later in life. Most young people diagnosed with FRDA require mobility aids such as a cane, walker or wheelchair by their teens or early twenties. As the disease progresses, patients lose their sight and hearing. Other complications include scoliosis and diabetes mellitus.

This condition is caused by mutations in the frataxin (FXN) gene. The ataxia of FRDA 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 myelin sheath. Diagnosis is based on physical symptoms and patient history and is confirmed by genetic testing.

There is currently no cure or effective treatment. FRDA can shorten life expectancy, and heart disease is the most common cause of death. However, people with less severe features of FA live into their sixties or older.

FRDA affects 1 in 50,000 people in the United States and is the most common inherited ataxia. Rates are highest in people of Western European descent. The condition is named after the German physician Nikolaus Friedreich, who first described the condition in the 1860s.[1]

Signs and symptoms

Symptoms typically present between the ages of 5 and 15 years, but in Late Onset FRDA they may occur in the patient's 20s or 30s. The progressive loss of coordination and muscle strength leads to motor incapacitation and the full-time use of a wheelchair. Most young people diagnosed with FRDA require mobility aids such as a cane, walker, or wheelchair by their teens or early 20s.[2]

The disease is progressive with increasing staggering or stumbling gait and frequent falling. Lower extremities are more severely involved. Long-term observation shows that many patients reach a plateau in symptoms in the patient's early adulthood. On average, after 10–15 years with the disease, patients lose the ability to stand or walk without assistance. However, disease progression is variable, and patients may be ambulatory decades after onset, while others require the use of a wheelchair within a few years.[2]

Symptoms may include the following:

  • Muscle weakness in the arms and legs
  • Cerebellar: nystagmus, fast saccadic eye movements, dysmetria, Loss of coordination (truncal ataxia, Stomping gait)
  • Vision impairment
  • Hearing impairment
  • Slurred speech[3]
  • Curvature of the spine
  • High plantar arches
  • About 20% of patients develop carbohydrate intolerance and 10% develop diabetes mellitus.[4]
  • Lower motor neuron lesion: absent deep tendon reflexes.
  • Pyramidal: extensor plantar responses, and distal weakness.
  • Dorsal column: Loss of vibratory sensation and proprioceptive sensation occurs.
  • Cardiac involvement occurs in 91% of patients, including cardiomegaly (up to dilated cardiomyopathy), symmetrical hypertrophy, heart murmurs, atrial fibrillation, tachycardia (fast heart rate), hypertrophic cardiomyopathy) and conduction defects.

Causes

FRDA is an autosomal recessive disorder that affects a gene (FXN) on chromosome 9 which produces an important protein called frataxin.[5]

The exact role of frataxin in normal physiology remains unclear.[6] Frataxin is an iron-binding protein responsible for forming iron-sulfur clusters. One result of frataxin deficiency is mitochondrial iron overload, which damages many proteins as well as fatigue due to effects on cellular metabolism.[5]

In 96% of cases the mutant FXN gene has 90-1,300 GAA trinucleotide repeat expansions in intron 1 of both alleles.[7] This expansion causes epigenetic changes and leads to the formation of heterochromatin in the vicinity of the repeat.[5] The length of the GAA repeat is correlated with age of onset.[8] The formation of heterochromatin results in reduced transcription of the gene and low levels of frataxin.[9]

In about 4% of cases the disease is caused by a (missense, nonsense, or intronic) point mutation, where the patient is heterozygotes with an expansion in one allele and a point mutation in the other.[10] A missense point mutation can have milder symptoms.[11] A detailed genetic work up is needed to determine this diagnosis.[12]

Pathophysiology

The ataxia of FRDA 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 myelin sheath.

The primary site of pathology is in the spinal cord and peripheral nerves. Sclerosis and degeneration of dorsal root ganglion, spinocerebellar tracts, lateral corticospinal tracts, and posterior columns.[13] The motor neurons of the spinal cord are spared. In peripheral nerves there is a loss of large myelinated fibers.

Progressive destruction of dorsal root ganglia account for thinning of dorsal roots, degeneration of dorsal columns, transsynaptic atrophy of nerve cells in Clarke's column and dorsal spinocerebellar fibers, atrophy of gracile and cuneate nuclei and neuropathy of sensory nerves. The lesion of the dentate nucleus consists of progressive and selective atrophy of large glutamatergic neurons and grumose degeneration of corticonuclear synaptic terminals that contain gamma-aminobutyric acid (GABA). Small GABAergic neurons and their projection fibers in the dentato-olivary tract survive. Atrophy of Betz cells and corticospinal tracts constitute a second lesion.{{citation needed|date=July 2017}}

Frataxin has a variety of known functions. Frataxin assists iron-sulfur protein synthesis in the electron transport chain to ultimately generate adenosine triphosphate (ATP), the energy molecule necessary to carry out metabolic functions in cells. Frataxin also regulates iron transfer in the mitochondria by providing a proper amount of reactive oxygen species (ROS) to maintain normal processes.[14] Without frataxin, the energy in the mitochondria falls, and excess iron causes extra ROS to be created, leading to further cell damage.[18][14] Low frataxin levels lead to insufficient biosynthesis of iron–sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase and iron dysmetabolism of the entire cell. This globular protein consists of two α helices and seven β strands and is highly conserved, occurring in eukaryotes and some prokaryotes.[15]

Mitochondrial DNA (mtDNA) is especially exposed to attack by Reactive oxygen species since both are located within the mitochondria. Because several enzymes of the electron transport chain are encoded in mtDNA, ROS-induced damage to mtDNA may cause further increases in ROS production and oxidative stress. Patient and FRDA mouse model fibroblasts have elevated levels of DNA double-strand breaks.[16] Using a lentivirus gene delivery system to deliver the frataxin gene to FRDA patient and mouse model cells, it was possible to obtain long-term over-expression of frataxin mRNA and frataxin protein levels. This over-expression was associated with a substantially reduced level of DNA double-strand breaks.[16] Frataxin is normally involved in the repair of DNA damage, which may be important for preventing neurodegeneration.[16]

Diagnosis and monitoring

A diagnosis requires investigation of the medical history and a thorough physical examination, in particular, looking for balance difficulty, loss of proprioception, an absence of reflexes, and signs of other neurological problems.

Tests that may aid in the diagnosis or management of the disorder include:

  • Electromyogram (EMG), which measures the electrical activity of muscle cells
  • Nerve conduction studies, which measure the speed with which nerves transmit impulses
  • Electrocardiogram (ECG), which gives a graphic presentation of the electrical activity or beat pattern of the heart
  • Echocardiogram, which records the position and motion of the heart muscle
  • Blood tests to check for elevated glucose levels and vitamin E levels
  • X-ray radiograph for scoliosis[12]
  • Magnetic resonance imaging (MRI) or computed tomography (CT) scans, tests which provide brain and spinal cord images that are useful for ruling out other neurological conditions[17]
Genetic testing provides a conclusive diagnosis.[17]

Other diagnoses include Charcot-Marie-Tooth type 1 and 2, ataxia with vitamin E deficiency, ataxia-oculomotor apraxia type 1 and 2 and other early-onset ataxias.[18]

Management

There is no FDA-approved disease-modifying agent to correct FRDA at the genetic or cellular level.[28] While this is an inherited disease, there is a significant delay in symptom onset (7–10 years or greater in most cases) and the disease progresses slowly. This window may be a treatment window for therapies. [19]

Rehabilitation

Rehabilitation therapy is a cornerstone of present-day ataxia therapy and there is evidence that this therapy improves symptoms in the short-term and that, with continued exercise, benefits can be maintained long-term.[19]

Physical therapy should consist of intensive motor coordination, balance, and stabilization training. To address the ataxic gait pattern and loss of proprioception typically seen in patients, physical therapists can use visual cueing during gait training to help facilitate a more efficient gait pattern.[20] Frenkel exercises and PNF techniques were developed to improve proprioception.[19]

Low intensity strengthening exercises should be incorporated to maintain functional use of the upper and lower extremities.[21] Stabilization exercises of the trunk and low back can help with postural control and the management of scoliosis,[20] especially if the person is non-ambulatory and requires the use of a wheelchair. Stretching and muscle relaxation exercises can be prescribed to help manage spasticity and prevent deformities.[21] Other goals can be set according to the needs and wishes of the patient, including increased transfer and locomotion independence; muscle strengthening; increased physical resilience; “safe fall” strategy; learning to use mobility aids; learning how to reduce the body’s energy expenditure; and developing specific breathing patterns.[36]

Outside therapy, patients should be encouraged to keep up continuous coordination and balance training to preserve gains.[22]

Balance and coordination training using visual feedback can be incorporated into activities of daily living. Exercises should reflect functional tasks such as cooking, transfers and self-care.[20]

Video game therapy, or exergaming, is a promising new tool for the treatment of FRDA. Physiotherapy exercises complemented by whole-body and coordinative training on video games have been found to be beneficial for early onset and advanced patients. Video game-based training involves motivational reward incentives and exercise environments that can stimulate and train patients’ real-world activities and anticipatory coordination capacities. Many patients find video games to be a convenient, cost-effective, and motivational way to engage in rehabilitation exercises.[19]

Speech therapy

Patients often undertake speech therapy since dysarthria occurs in almost all patients. However, the dysarthria is not always ataxic and the dysarthria can be mixed. The speech intelligibility can be mild to severely reduced. Speech therapy seeks to improve speech outcomes and/or compensate for communication deficits.[23] Dysphagia (difficulty swallowing) is a common symptom of Friedreich's ataxia, and speech therapy can support patients to eat and drink in a safer way.[24]

Devices

Good quality, well-fitted orthoses can support normal joint alignment, promote correct posture, stabilize joints during walking, and improve range of motion. This is important to help manage spasticity, and to prevent foot deformities and scoliosis.[2]

There is evidence that devices for electrical stimulation, such as functional electrical stimulation or transcutaneous nerve stimulation, may help alleviate symptoms.[2]

Wearable proprioceptive stabilizers like the Equistasi are neurological rehabilitation devices meant to exert focal mechanical vibration on muscles and joints. Research indicates that this may improve limb and gait ataxia in patients and similar conditions.[25]

Orthopedic shoes improve gait in ambulatory individuals.[26] In severe cases in which the rehabilitation treatment applications are insufficient, use of supportive devices enables the patient to function more easily within the present functional level.[27] As progression of ataxia occurs, assistive devices such as a cane, walker, or wheelchair may be 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.

Medication

Although there are no curative pharmacological therapies, many of its side effects respond well to medication. In particular, the cardiac abnormalities can often be controlled with ACE inhibitors such as enalapril, ramipril, lisinopril or trandolapril, sometimes used in conjunction with beta blockers. Patients with symptomatic heart failure might be prescribed eplerenone or digoxin to keep cardiac abnormalities under control.[26]

Surgery

Patients may require surgical interventions with the aim to help the patient maintain functional independence for as long as possible.

If physical and pharmacological interventions are ineffective, surgical solutions may be considered to correct deformities caused by abnormal muscle tone. Titanium screws and rods inserted in the spine help prevent or slow the progression of scoliosis. In patients suffering from the equinus deformity, surgically lengthening the Achilles tendon is shown to improve independence and mobility.[26]

Patients experiencing severe heart failure that does not respond to maximal medical management may be considered for implantation of an automated implantable cardioverter-defibrillator or, in cases, a cardiac transplant.[26]

Prognosis

Every patient has a particular form of evolution of the disease.[27] In general, patients who were younger at diagnosis, and those with longer GAA triplet expansions, tend to have more severe symptoms.[26] Studies investigating FRDA have often provided inconclusive and contradicting results arising from inhomogeneity in trial populations, non validated measures used in older studies,[19] and low availability of study participants[28] The use and development of model clinical instruments and technologies such as computerized gait monitoring, speech evaluation, and imaging with molecular indices should add precision and new avenues for capturing ataxic symptoms and physiologic functions, thereby resulting in more precise and extended measurement of disease progression.[19]

Congestive heart failure and cardiac arrhythmia are the leading cause of death.[29] However, people with less severe features of FRDA live into their sixties or older.[17]

Epidemiology

FRDA is the most prevalent inherited ataxia,[30] affecting about 1 in 50,000 people in the United States. Males and females are affected equally. The estimated carrier prevalence is 1:100.[26]

A 1990-1996 study of Europeans calculated the incidence rate was 2.8:100,000.[31] A later study estimated prevalence of 3-4 cases per 100,000 individuals.[32]

A nationwide epidemiological study of Japanese patients with on spinocerebellar degeneration reported that the percentage of patients was 2.4%. Making the prevalence rate of FRDA 0.1:100,000.[33]

Haplogroup R1b

FRDA follows the same pattern as haplogroup R1b. Haplogroup R1b is the most frequently occurring paternal lineage in Western Europe. FRDA and Haplogroup R1b are more common in northern Spain, Ireland and France, rare in Russia and Scandinavia, and follow a gradient through central and eastern Europe. A population carrying the disease went through a population bottleneck in the Franco-Cantabrian region during the last ice age. [34]

History

The condition is named after the German pathologist and neurologist, Nikolaus Friedreich, who first described the condition in the 1860s.[35] Friedreich reported five patients with the condition in a series of three papers in 1863 at the University of Heidelberg.[36][37][38] Further observations appeared in a paper in 1876.[39]

FRDA was first linked to a GAA repeat expansion on chromosome 9 in 1996.[40]

Frantz Fanon wrote his medical thesis on FRDA, in 1951.[41]

The FXN gene was identified by an international team in 1996.[42]

A 1984 Canadian study was able to trace 40 cases 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.[43]

Research

  • RG2833, a histone deacetylase inhibitor developed by Repligen, was acquired by BioMarin Pharmaceutical in January 2014.[44] A phase Ib clinical trial with RG2833 was completed in 2014 and research continues.[73]
  • Protection of cells from damage with the use of deuterated compounds was attempted by Retrotope. Its first drug RT001 is a deuterated synthetic homologue of ethyl linoleate, a polyunsaturated fatty acid (11,11-D2-ethyl linoleate) or (PUFAs). (PUFAs) are the major component of lipid membranes, particularly in mitochondria. Their high susceptibility to oxidation by reactive oxygen species through the chain reaction can be substantially reduced by the replacement of hydrogen (H) atoms with the isotope deuterium (D), yielding D-PUFAs. RT001 was compared with non-deuterated linoleic acid ethyl ester in a randomized, double-blind, controlled trial in 18 patients for 4 weeks.[45] Primary endpoints were safety, tolerability, and pharmacokinetics. Secondary endpoints included the FARS, a timed foot-walk test and cardiopulmonary exercise testing. The study met its primary safety and tolerability endpoints.[46] An improvement in peak workload and VO2 max in the RT001 group compared to placebo, as well as a positive trend in the neurological scales in the drug group were detected.
  • Research in gene therapy is another treatment under development. One study in mouse models showed that gene replacement therapy completely reversed the cardiac symptoms at the functional, cellular, and molecular levels.[19]

Discontinued efforts

  • Nicotinamide (vitamin B3) represents was found effective in preclinical FRDA models and well-tolerated by patients. An open-label, dose-escalation study demonstrated that higher doses boosted frataxin expression and attenuated abnormal heterochromatin, but failed to establish any clinical benefit in a study of 12 months.[47]
  • A Cochrane review on treatment of patients with antioxidants concluded that there is limited but not persuasive evidence of efficacy.[48] An antioxidant Idebenone was removed from the Canadian market in 2013 due to lack of effectiveness.[49]
  • Horizon Pharma's development plan of interferon gamma-1B for treatment of FRDA was given fast track designation by the Food and Drug Administration in 2015.[50] However, in the Phase 3 trial released in December 2016, the results did not meet primary endpoints.[51]

Society and culture

The Cake Eaters is a 2007 independent drama film that stars Kristen Stewart as a young woman with a severe case of FRDA.[52]The Ataxian is a documentary that tells the story of Kyle Bryant, an athlete with FRDA who completes a long-distance bike race in an adaptive "trike" to raise money for research.[53]

Dynah Haubert is a lawyer with FRDA who works for Disability Rights Pennsylvania (DRP). She spoke at the 2016 Democratic National Convention about her support for Hillary Clinton and her work supporting Americans with disabilities.[54]

Geraint Williams in an athlete affected by FRDA who is known for scaling Mount Kilimanjaro in an adaptive wheelchair known as a Mountain Trike.[55]

Shobhika Kalra is an activist with FRDA who helped build over 1000 wheelchair ramps across the UAE.[56] With her sister, she founded Wings of Angelz, a social initiative that uses an app to collect data about accessibility in public places. Their goal is to make Dubai fully wheelchair-friendly by 2020.

External links

  • Friedreich's Ataxia Research Alliance
  • [https://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
  • {{NINDS|National Institute of Neurological Disorders website}}
  • {{GeneTests|friedreich}}

References

1. ^{{WhoNamedIt|synd|1406}}
2. ^{{cite journal | vauthors = Pandolfo M | title = Friedreich ataxia: the clinical picture | journal = Journal of Neurology | volume = 256 Suppl 1 | issue = 1 Suppl | pages = 3–8 | date = March 2009 | pmid = 19283344 | doi = 10.1007/s00415-009-1002-3 }}
3. ^{{cite web|url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Friedreichs-Ataxia-Fact-Sheet|title = Friedreich Ataxia Fact Sheet|accessdate= February 10, 2019}}
4. ^{{cite journal | vauthors = Thoren C | title = Diabetes mellitus in Friedreich's ataxia | journal = Acta Paediatrica. Supplementum | volume = 135 | pages = 239–47 | date = June 1962 | pmid = 13921008 | doi = 10.1111/j.1651-2227.1962.tb08680.x }}
5. ^1 2 {{cite journal | vauthors = Klockgether T | title = Update on degenerative ataxias | journal = Current Opinion in Neurology | volume = 24 | issue = 4 | pages = 339–45 | date = August 2011 | pmid = 21734495 | doi = 10.1097/WCO.0b013e32834875ba }}
6. ^{{cite journal|doi = 10.1016/j.brainresrev.2011.04.001 |pmid = 21550666 |title = Friedreich's ataxia: Past, present and future |journal = Brain Research Reviews |volume = 67 |issue = 1–2 |pages = 311–330 |year = 2011 |last1 = Marmolino |first1 = Daniele }}
7. ^{{cite journal |title=Role of frataxin protein deficiency and metabolic dysfunction in Friedreich ataxia, an autosomal recessive mitochondrial disease | vauthors=Clark E, Johnson J, Dong YN, Mercado-Ayon, Warren N, Zhai M, McMillan E, Salovin A, Lin H, Lynch DR |journal=Neuronal Signaling |date=Nov 2018 |doi=10.1042/NS20180060 |url=http://www.neuronalsignaling.org/content/2/4/NS20180060.full |accessdate=1 April 2019}}
8. ^{{cite journal |last1=Durr |doi=10.1056/nejm199610173351601|pmid=8815938|title=Clinical and Genetic Abnormalities in Patients with Friedreich's Ataxia|journal=New England Journal of Medicine|volume=335|issue=16|pages=1169–1175|year=1996}}
9. ^{{cite journal | vauthors = Montermini L, Andermann E, Labuda M, Richter A, Pandolfo M, Cavalcanti F, Pianese L, Iodice L, Farina G, Monticelli A, Turano M, Filla A, De Michele G, Cocozza S | title = The Friedreich ataxia GAA triplet repeat: premutation and normal alleles | journal = Human Molecular Genetics | volume = 6 | issue = 8 | pages = 1261–6 | date = August 1997 | pmid = 9259271 | doi = 10.1093/hmg/6.8.1261 }}
10. ^{{cite journal |doi=10.1002/1531-8249(199902)45:2<200::AID-ANA10>3.0.CO;2-U|title=Friedreich's ataxia: Point mutations and clinical presentation of compound heterozygotes|journal=Annals of Neurology|volume=45|issue=2|pages=200–206|year=1999|last1=Cosse|first1=Mireille|last2=dRr|first2=Alexandra|last3=Schmitt|first3=Michele|last4=Dahl|first4=Niklas|last5=Trouillas|first5=Paul|last6=Allinson|first6=Patricia|last7=Kostrzewa|first7=Markus|last8=Nivelon-Chevallier|first8=Annie|last9=Gustavson|first9=Karl-Henrik|last10=KohlschTter|first10=Alfried|last11=miLler|first11=Ulrich|last12=Mandel|first12=Jean-Louis|last13=Brice|first13=Alexis|last14=Koenig|first14=Michel|last15=Cavalcanti|first15=Francesca|last16=Tammaro|first16=Angela|last17=De Michele|first17=Giuseppe|last18=Filla|first18=Alessandro|last19=Cocozza|first19=Sergio|last20=Labuda|first20=Malgorzata|last21=Montermini|first21=Laura|last22=Poirier|first22=Jose|last23=Pandolfo|first23=Massimo}}
11. ^{{cite journal |doi=10.1002/1531-8249(199902)45:2<200::AID-ANA10>3.0.CO;2-U|title=Friedreich's ataxia: Point mutations and clinical presentation of compound heterozygotes|journal=Annals of Neurology|volume=45|issue=2|pages=200–206|year=1999|last1=Cosse|first1=Mireille|last2=dRr|first2=Alexandra|last3=Schmitt|first3=Michle|last4=Dahl|first4=Niklas|last5=Trouillas|first5=Paul|last6=Allinson|first6=Patricia|last7=Kostrzewa|first7=Markus|last8=Nivelon-Chevallier|first8=Annie|last9=Gustavson|first9=Karl-Henrik|last10=KohlschTter|first10=Alfried|last11=mLler|first11=Ulrich|last12=Mandel|first12=Jean-Louis|last13=Brice|first13=Alexis|last14=Koenig|first14=Michel|last15=Cavalcanti|first15=Francesca|last16=Tammaro|first16=Angela|last17=De Michele|first17=Giuseppe|last18=Filla|first18=Alessandro|last19=Cocozza|first19=Sergio|last20=Labuda|first20=Malgorzata|last21=Montermini|first21=Laura|last22=Poirier|first22=Jose|last23=Pandolfo|first23=Massimo}}
12. ^1 {{cite journal |doi=10.1177/0883073812448440|pmid=22752491|pmc=3674546|title=Novel Diagnostic Paradigms for Friedreich Ataxia|journal=Journal of Child Neurology|volume=27|issue=9|pages=1146–1151|year=2012|last1=Brigatti|first1=Karlla W.|last2=Deutsch|first2=Eric C.|last3=Lynch|first3=David R.|last4=Farmer|first4=Jennifer M.}}
13. ^{{cite journal | vauthors = Delatycki MB, Williamson R, Forrest SM | title = Friedreich ataxia: an overview | journal = Journal of Medical Genetics | volume = 37 | issue = 1 | pages = 1–8 | date = January 2000 | pmid = 10633128 | pmc = 1734457 | doi = 10.1136/jmg.37.1.1 }}
14. ^1 {{cite journal | vauthors = Sahdeo S, Scott BD, McMackin MZ, Jasoliya M, Brown B, Wulff H, Perlman SL, Pook MA, Cortopassi GA | title = Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia | journal = Human Molecular Genetics | volume = 23 | issue = 25 | pages = 6848–62 | date = December 2014 | pmid = 25113747 | pmc = 4245046 | doi = 10.1093/hmg/ddu408 }}
15. ^1 {{cite journal | vauthors = Pandolfo M | title = Friedreich ataxia | journal = Archives of Neurology | volume = 65 | issue = 10 | pages = 1296–303 | date = October 2008 | pmid = 18852343 | doi = 10.1001/archneur.65.10.1296 }}
16. ^1 2 {{cite journal |vauthors=Khonsari H, Schneider M, Al-Mahdawi S, Chianea YG, Themis M, Parris C, Pook MA, Themis M |title=Lentivirus-meditated frataxin gene delivery reverses genome instability in Friedreich ataxia patient and mouse model fibroblasts |journal=Gene Ther. |volume=23 |issue=12 |pages=846–856 |date=December 2016 |pmid=27518705 |pmc=5143368 |doi=10.1038/gt.2016.61 |url=}}
17. ^1 2 {{cite web|title=Friedreich's Ataxia Fact Sheet |publisher=National Institute of Neurological Disorders and Stroke|url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Friedreichs-Ataxia-Fact-Sheet}} {{PD-notice}}
18. ^{{cite web |title=Friedreich ataxia NIH page |url=https://rarediseases.info.nih.gov/diseases/6468/friedreich-ataxia |website=NIH Rare diseases |accessdate=March 17, 2019}}
19. ^1 2 3 4 5 6 7 {{cite journal |vauthors = Aranca TV, Jones TM, Shaw JD, Staffetti JS, Ashizawa T, Kuo SH, Fogel BL, Wilmot GR, Perlman SL, Onyike CU, Ying SH, Zesiewicz TA|title=Emerging therapies in Friedreich's ataxia |journal=Neurodegenerative Disease Management |date=Feb 2016 |pmid=26782317 |pmc=4768799 |volume=6 | issue = 1|pages=49–65| doi = 10.2217/nmt.15.73 }}
20. ^1 2 {{cite journal | title = Holding Steady: How physical therapy can help patients with Friedreich's Ataxia | journal = Advance | date = 2007-01-01 | first = Wendy | last = Powers | volume = 18 | issue = 1 | page = 26 | id = | url = http://www.fortnet.org/fapg/PTarticleFA.htm | access-date = 2011-05-16 | deadurl = yes | archive-url = https://web.archive.org/web/20110726071056/http://www.fortnet.org/fapg/PTarticleFA.htm | archive-date = 2011-07-26 | df = }}
21. ^1 {{cite web | url = http://www.mdausa.org/publications/fa-fried-qa.html | title = Facts About Friedreich's Ataxia (FA) | access-date = 2011-05-16 | year = 2011 | work = Muscular Dystrophy Association | deadurl = yes | archive-url = https://web.archive.org/web/20110927111223/http://www.mdausa.org/publications/fa-fried-qa.html | archive-date = 2011-09-27 | df = }}
22. ^1 {{cite book |vauthors = Chien H, Barsottini O |title=Movement Disorders Rehabilitation |date=10 December 2016 |publisher=Springer, Cham |isbn=978-3-319-46062-8 |pages=83–95 |doi=10.1007/978-3-319-46062-8 }}
23. ^{{cite journal | vauthors = Vogel AP, Folker J, Poole ML | title = Treatment for speech disorder in Friedreich ataxia and other hereditary ataxia syndromes | journal = The Cochrane Database of Systematic Reviews | volume = 10 | issue = 10 | pages = CD008953 | date = October 2014 | pmid = 25348587 | doi = 10.1002/14651858.CD008953.pub2 | url = http://espace.library.uq.edu.au/view/UQ:706445/UQ706445_OA.pdf }}
24. ^{{cite journal | vauthors = Vogel AP, Brown SE, Folker JE, Corben LA, Delatycki MB | title = Dysphagia and swallowing-related quality of life in Friedreich ataxia | journal = Journal of Neurology | volume = 261 | issue = 2 | pages = 392–9 | date = February 2014 | pmid = 24371004 | doi = 10.1007/s00415-013-7208-4 }}
25. ^{{cite journal |vauthors = Leonardi L, Aceto MG, Marcotulli C, Arcuria G, Serrao M, Pierelli F, Paone P, Filla A, Roca A, Casali C|title=A wearable proprioceptive stabilizer for rehabilitation of limb and gait ataxia in hereditary cerebellar ataxias: a pilot open-labeled study |journal=Neurological Sciences |date=March 2017 |volume=38 |issue=3 |pages=459–463 |doi=10.1007/s10072-016-2800-x |pmid=28039539 }}
26. ^1 2 3 4 5 6 7 8 {{cite web |title=Friedreich ataxia clinical management guidelines |url=http://curefa.org/clinical-care-guidelines |year=2014 |publisher=Friedreich Ataxia Research Alliance (USA) |accessdate=23 October 2018}}
27. ^1 {{cite journal |vauthors = Ojoga F, Marinescu S |title=Physical Therapy and Rehabilitation for Ataxic Patients |journal=Balneo Research Journal |date=2013 |volume=4 |issue=2 |pages=81–84 |doi=10.12680/balneo.2013.1044 |url=https://www.ingentaconnect.com/content/doaj/20697597/2013/00000004/00000002/art00002}}
28. ^{{cite journal |vauthors = Michele GD, Filla A|title=Friedreich ataxia today—preparing for the final battle |journal=Nature Reviews Neurology |date=October 2015 |volume=11 |issue=4 |pages = 188–190 |doi=10.1038/nrneurol.2015.33 |pmid=25752951 }}
29. ^{{cite journal |title=Demographic and clinical features and rehabilitation outcomes of patients with Friedreich ataxia: A retrospective study |journal=Y Turkish Society of Physical Medicine and Rehabilitation |date=January 2018 |volume=64 |issue=3 |pages=230–238 |doi=10.5606/tftrd.2018.2213 |url=http://ftrdergisi.com/uploads/pdf/pdf_4066.pdf|last1=Doğan-Aslan |first1=Meryem }}
30. ^{{cite journal | vauthors = Lodi R, Tonon C, Calabrese V, Schapira AH | title = Friedreich's ataxia: from disease mechanisms to therapeutic interventions | journal = Antioxidants & Redox Signaling | volume = 8 | issue = 3–4 | pages = 438–43 | year = 2006 | pmid = 16677089 | doi = 10.1089/ars.2006.8.438 }}
31. ^{{cite journal |doi=10.1056/NEJM199610173351601|pmid=8815938|title=Clinical and Genetic Abnormalities in Patients with Friedreich's Ataxia|journal=New England Journal of Medicine|volume=335|issue=16|pages=1169–1175|year=1996|last1=Dürr|first1=Alexandra|last2=Cossée |first2=Mireille|last3=Agid|first3=Yves|last4=Campuzano|first4=Victoria|last5=Mignard|first5=Claude|last6=Penet|first6=Christiane|last7=Mandel|first7=Jean-Louis|last8=Brice|first8=Alexis|last9=Koenig|first9=Michel}}
32. ^{{cite journal |doi=10.1038/nrneurol.2009.26|pmid=19347027|title=Diagnosis and treatment of Friedreich ataxia: A European perspective|journal=Nature Reviews Neurology|volume=5|issue=4|pages=222–234|year=2009|last1=Schulz|first1=Jörg B.|last2=Boesch|first2=Sylvia|last3=Bürk|first3=Katrin|last4=Dürr|first4=Alexandra|last5=Giunti|first5=Paola|last6=Mariotti|first6=Caterina|last7=Pousset|first7=Francoise|last8=Schöls|first8=Ludger|last9=Vankan|first9=Pierre|last10=Pandolfo|first10=Massimo}}
33. ^{{cite journal |last1=Kita |first1=K. |title=Spinocerebellar degeneration in Japan--the feature from an epidemiological study |journal=Clinical Neurology |date=1993 |volume=33 |issue=12 |pages=1279–1284}}
34. ^{{cite journal | vauthors = Vankan P | title = Prevalence gradients of Friedreich's ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge | journal = Journal of Neurochemistry | volume = 126 Suppl 1 | pages = 11–20 | date = August 2013 | pmid = 23859338 | doi = 10.1111/jnc.12215 | bibcode = 2006JNeur..26.9606G }}
35. ^{{WhoNamedIt|synd|1406}}
36. ^{{cite journal | vauthors=Friedreich N | title=Ueber degenerative Atrophie der spinalen Hinterstränge |trans-title=About degenerative atrophy of the spinal posterior column |language=German | journal=Arch Pathol Anat Phys Klin Med | volume=26 | issue=3–4 | pages=391–419 | year=1863 | doi=10.1007/BF01930976 }}
37. ^{{cite journal | vauthors=Friedreich N | title=Ueber degenerative Atrophie der spinalen Hinterstränge |trans-title=About degenerative atrophy of the spinal posterior column |language=German | journal=Arch Pathol Anat Phys Klin Med | volume=26 | issue=5–6 | pages=433–459 | year=1863 | doi=10.1007/BF01878006 }}
38. ^{{cite journal | vauthors=Friedreich N | title=Ueber degenerative Atrophie der spinalen Hinterstränge |trans-title=About degenerative atrophy of the spinal posterior column |language=German | journal=Arch Pathol Anat Phys Klin Med | volume=27 | issue= 1–2| pages=1–26 | year=1863 | doi=10.1007/BF01938516 }}
39. ^{{cite journal | vauthors=Friedreich N | title=Ueber Ataxie mit besonderer Berücksichtigung der hereditären Formen |trans-title=About ataxia with special reference to hereditary forms |language=German | journal=Arch Pathol Anat Phys Klin Med | volume=68 | issue=2 | pages=145–245 | year=1876 | doi=10.1007/BF01879049 }}
40. ^{{cite journal | vauthors = Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Cañizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, De Michele G, Filla A, De Frutos R, Palau F, Patel PI, Di Donato S, Mandel JL, Cocozza S, Koenig M, Pandolfo M | title = Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion | journal = Science | volume = 271 | issue = 5254 | pages = 1423–7 | date = March 1996 | pmid = 8596916 | doi = 10.1126/science.271.5254.1423 | bibcode = 1996Sci...271.1423C }}
41. ^Adam Shatz, "Where Life Is Seized", London Review of Books, 19 January 2017
42. ^{{cite journal |last1=Campuzano |first1=V. |last2=Montermini |first2=L. |last3=Moltò |first3=MD |title=Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion |journal=Science |date=March 1996 |volume=271 |issue=5254 |pages=1423–1427|bibcode=1996Sci...271.1423C |doi=10.1126/science.271.5254.1423 }}
43. ^{{cite journal | vauthors = 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 | volume = 11 | issue = 4 Suppl | pages = 506–9 | date = November 1984 | pmid = 6391645 | doi = 10.1017/S0317167100034971}}
44. ^{{cite web |url=http://investors.bmrn.com/releasedetail.cfm?ReleaseID=820213 |title=BioMarin Announces Agreement With Repligen for Pre-clinical Compounds (NASDAQ:BMRN) |publisher=Investors.bmrn.com |date=2014-01-21 |access-date=2015-07-04 |archive-url=https://web.archive.org/web/20150705183749/http://investors.bmrn.com/releasedetail.cfm?ReleaseID=820213 |archive-date=2015-07-05 |dead-url=yes |df= }}
45. ^{{cite journal | vauthors = Indelicato E, Bosch S | title = Emerging therapeutics for the treatment of Friedreich's ataxia | journal = Expert Opinion on Orphan Drugs | volume = 6 | pages = 57–67 | date = 2018 | pmid = | doi = 10.1080/21678707.2018.1409109 }}
46. ^{{cite journal | vauthors = Zesiewicz T, Heerinckx F, De Jager R, Omidvar O, Kilpatrick M, Shaw J, Shchepinov MS | title = Randomized, clinical trial of RT001: Early signals of efficacy in Friedreich's ataxia | journal = Movement Disorders | volume = 6 | issue = 1 | pages = 57–67 | date = April 2018 | pmid = 29624723 | doi = 10.1002/mds.27353 }}
47. ^1 {{cite journal | vauthors = Bürk K | title = Friedreich Ataxia: current status and future prospects | journal = Cerebellum & Ataxias | volume = 4 | page = 4 | year = 2017 | pmid = 28405347 | pmc = 5383992 | doi = 10.1186/s40673-017-0062-x }}
48. ^{{cite journal | vauthors = Kearney M, Orrell RW, Fahey M, Brassington R, Pandolfo M | title = Pharmacological treatments for Friedreich ataxia | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD007791 | date = August 2016 | pmid = 27572719 | doi = 10.1002/14651858.CD007791.pub4 | url = http://discovery.ucl.ac.uk/1514853/1/Kearney_et_al-2016-The_Cochrane_Library.pdf }}
49. ^{{cite web|url=http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/23519a-eng.php |title=CATENA (idebenone) - Voluntary withdrawal of CATENA from the Canadian market - For the Public - Recalls & alerts - Healthy Canadians Website |publisher=Healthycanadians.gc.ca |date= |access-date=2015-07-04}}
50. ^{{cite news | last=Dulaney |first=Chelsey |url=https://www.wsj.com/articles/horizon-pharmas-friedreichs-ataxia-drug-gets-fast-track-designation-1428665791 |title=Horizon Pharma’s Friedreich’s Ataxia Drug Gets Fast-Track Designation |publisher= The Wall Street Journal|date=2015-04-10 |access-date=2015-07-04}}
51. ^{{cite news |last1=Taylor |first1=Nick Paul |title=Horizon slumps after phase 3 Friedreich's ataxia trial flops |url=https://www.fiercebiotech.com/biotech/horizon-slumps-after-phase-3-friedreich-s-ataxia-trial-flops |accessdate=December 11, 2018 |publisher=Fierce Biotech |date=December 8, 2016}}
52. ^{{cite news | first=Stephen | last=Holden | coauthors= |authorlink= | title=The Cake Eaters | date=March 13, 2009 | publisher= | url =https://movies.nytimes.com/2009/03/13/movies/13cake.html?partner=Rotten%20Tomatoes&ei=5083 | work =The New York Times | pages = | accessdate = 2009-07-08 | language = }}
53. ^{{cite news|url=http://sacramento.cbslocal.com/2015/05/30/devastating-diagnosis-pushes-local-man-to-live-bigger/ |title=Devastating Diagnosis Pushes Local Man To Live Bigger |work=CBS Sacramento |date=2015-05-30 |accessdate=2015-06-12}}
54. ^{{cite web |title=How the DNC Is Subtly Rebuking Donald Trump's Mockery of a Disabled Reporter |url=https://slate.com/human-interest/2016/07/dnc-rebukes-trump-for-mocking-the-disabled.html |website=Slate|date=2016-07-27 }}
55. ^{{cite web |title=Man with rare nerve condition climbs Mount Kilimanjaro to raise money for charity |url=https://www.itv.com/news/wales/2018-11-25/man-with-rare-nerve-condition-climbs-mount-kilimanjaro-to-raise-money-for-charity/ |website=ITV |accessdate=14 December 2018}}
56. ^{{cite web |title=Shobhika Kalra: Meet the Dubai woman in wheelchair who helped build 1,000 ramps across UAE |url=https://gulfnews.com/world/shobhika-kalra-meet-the-dubai-woman-in-wheelchair-who-helped-build-1000-ramps-across-uae-1.2295954 |website=GULF NEWS}}
{{Medical resources
| DiseasesDB = 4980
| ICD10 = {{ICD10|G|11|1|g|10}}
| ICD9 = {{ICD9|334.0}}
| OMIM = 229300
| MedlinePlus = 001411
| eMedicineSubj = article
| eMedicineTopic = 1150420
| MeshID = D005621
| GeneReviewsNBK = NBK1281
| GeneReviewsName = Friedreich Ataxia
| Orphanet = 95
}}{{Diseases of the nervous system}}{{Mitochondrial diseases}}{{Trinucleotide repeat disorders}}{{Authority control}}{{DEFAULTSORT:Friedreich's Ataxia}}

5 : Systemic atrophies primarily affecting the central nervous system|Autosomal recessive disorders|Mitochondrial diseases|Trinucleotide repeat disorders|Rare diseases
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/9/23 18:18:49