wikipedia - friedreich's ataxia (checked).pdf

7/24/2019 Wikipedia - Friedreich's ataxia (CHECKED).pdf

1/8

7/17/15, riedreich's ataxia - Wikipedia, the free encyclopedia

Page ttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia

Friedreich's ataxia

Frataxin

Classification and external resources

ICD-10 G11.1

(http://apps.who.int/classifications/icd10/browse/2015/en#/G11

ICD-9-CM 334.0 (http://www.icd9data.com/getICD9Code.ashx?icd9=334

OMIM 229300 (http://omim.org/entry/229300)

DiseasesDB 4980 (http://www.diseasesdatabase.com/ddb4980.htm)

MedlinePlus 001411

(http://www.nlm.nih.gov/medlineplus/ency/article/001411.htm

eMedicine article/1150420 (http://emedicine.medscape.com/article/11504

overview)

Patient UK Friedreich's ataxia (http://patient.info/doctor/friedreichs-ataxia

MeSH D005621 (https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?

field=uid&term=D005621)

GeneReviews Friedreich Ataxia

(http://www.ncbi.nlm.nih.gov/books/NBK1281/)

Friedreich's ataxiaFrom Wikipedia, the free encyclopedia

Friedreich's ataxiais an autosomal

recessive inherited disease that

causes progressive damage to the

nervous system. It manifests innitial symptoms of poor

coordination such as gait

disturbance; it can also lead to

scoliosis, heart disease and diabetes,

but does not affect cognitive

function. The disease progresses

until a wheelchair is required for

mobility. Its incidence in thegeneral

population is roughly 1 in 50,000.

The particular genetic mutation

expansion of an intronic GAA

riplet repeat in the FXN gene) leads

o reduced expression of the

mitochondrial protein frataxin. Over

ime this deficiency causes the

aforementioned damage, as well as

frequent fatigue due to effects on

cellular metabolism.

The ataxia of Friedreich's ataxiaresults 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 cordbecomes thinner and

nerve cells lose some of their myelin sheath (the insulating covering on some nerve cells that helps conduct

nerve impulses).

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

Contents

1 History2 Signs and symptoms
https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D005621https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D005621http://emedicine.medscape.com/article/1150420-overviewhttp://www.nlm.nih.gov/medlineplus/ency/article/001411.htmhttp://www.nlm.nih.gov/medlineplus/ency/article/001411.htmhttp://omim.org/entry/229300http://omim.org/entry/229300https://en.wikipedia.org/wiki/List_of_ICD-9_codeshttp://www.icd9data.com/getICD9Code.ashx?icd9=334.0http://www.icd9data.com/getICD9Code.ashx?icd9=334.0http://apps.who.int/classifications/icd10/browse/2015/en#/G11.1https://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.pnghttps://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.pnghttps://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.pnghttps://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.pnghttps://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.pnghttps://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.pnghttps://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.pnghttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Signs_and_symptomshttps://en.wikipedia.org/wiki/Myelin_sheathhttps://en.wikipedia.org/wiki/Cerebellumhttps://en.wikipedia.org/wiki/Nervous_tissuehttps://en.wikipedia.org/wiki/Spinal_cordhttps://en.wikipedia.org/wiki/Medical_Subject_Headingshttps://en.wikipedia.org/wiki/Degenerationhttps://en.wikipedia.org/wiki/Metabolismhttps://en.wikipedia.org/wiki/MedlinePlushttps://en.wikipedia.org/wiki/Scoliosishttps://en.wikipedia.org/wiki/Heart_diseasehttps://en.wikipedia.org/wiki/Diabetes_mellitushttps://en.wikipedia.org/wiki/Gait_disturbancehttps://en.wikipedia.org/wiki/Gait_disturbancehttps://en.wikipedia.org/wiki/Progressive_illnesshttps://en.wikipedia.org/wiki/Autosomal_recessivehttps://en.wikipedia.org/wiki/Inherited_diseasehttps://en.wikipedia.org/wiki/Autosomal_recessivehttps://en.wikipedia.org/wiki/Autosomal_recessivehttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Signs_and_symptomshttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Historyhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-1https://en.wikipedia.org/wiki/Nikolaus_Friedreichhttps://en.wikipedia.org/wiki/Germanyhttps://en.wikipedia.org/wiki/Nerve_impulseshttps://en.wikipedia.org/wiki/Myelin_sheathhttps://en.wikipedia.org/wiki/Cerebellumhttps://en.wikipedia.org/wiki/Spinal_cordhttps://en.wikipedia.org/wiki/Nervous_tissuehttps://en.wikipedia.org/wiki/Degenerationhttps://en.wikipedia.org/wiki/Ataxiahttps://en.wikipedia.org/wiki/Metabolismhttps://en.wikipedia.org/wiki/Frataxinhttps://en.wikipedia.org/wiki/Mitochondrialhttps://en.wikipedia.org/wiki/Diabetes_mellitushttps://en.wikipedia.org/wiki/Heart_diseasehttps://en.wikipedia.org/wiki/Scoliosishttps://en.wikipedia.org/wiki/Gait_disturbancehttps://en.wikipedia.org/wiki/Nervous_systemhttps://en.wikipedia.org/wiki/Progressive_illnesshttps://en.wikipedia.org/wiki/Inherited_diseasehttps://en.wikipedia.org/wiki/Autosomal_recessivehttp://www.ncbi.nlm.nih.gov/books/NBK1281/https://en.wikipedia.org/wiki/GeneReviewshttps://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&term=D005621https://en.wikipedia.org/wiki/Medical_Subject_Headingshttp://patient.info/doctor/friedreichs-ataxiahttps://en.wikipedia.org/wiki/Patient_UKhttp://emedicine.medscape.com/article/1150420-overviewhttps://en.wikipedia.org/wiki/EMedicinehttp://www.nlm.nih.gov/medlineplus/ency/article/001411.htmhttps://en.wikipedia.org/wiki/MedlinePlushttp://www.diseasesdatabase.com/ddb4980.htmhttps://en.wikipedia.org/wiki/Diseases_Databasehttp://omim.org/entry/229300https://en.wikipedia.org/wiki/OMIMhttp://www.icd9data.com/getICD9Code.ashx?icd9=334.0https://en.wikipedia.org/wiki/List_of_ICD-9_codeshttps://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problemshttp://apps.who.int/classifications/icd10/browse/2015/en#/G11.1https://en.wikipedia.org/wiki/ICD-10https://en.wikipedia.org/wiki/International_Statistical_Classification_of_Diseases_and_Related_Health_Problemshttps://en.wikipedia.org/wiki/Frataxinhttps://en.wikipedia.org/wiki/File:Protein_FXN_PDB_1ekg.png


2/8



3 Genetics4 Pathology

4.1 Pathogenesis5 Treatment

5.1 Idebenone5.2 RG28335.3 Nicotinamide5.4 In Research

6 Epidemiology7 In popular culture8 References9 External links

History

Friedreich, working as a professor of pathology at the University of Heidelberg, reported five patients with th

condition in a series of three papers in 1863.[2][3][4]Further observations appeared in a subsequent paper in1876.[5]

Signs and symptoms

Symptoms typically begin sometime between the ages of 5 to 15 years, but in Late Onset FA may occur in th

20s or 30s. Symptoms include any combination, but not necessarily all, of the following:

Muscle weakness in the arms and legs

Loss of coordinationVision impairmentHearing impairmentSlurred speechCurvature of the spine (scoliosis)High plantar arches (pes cavus deformity of the foot)Diabetes (about 20% of people with Friedreich's ataxia develop carbohydrate intolerance and 10%

develop diabetes mellitus)[6]

Heart disorders (e.g., atrial fibrillation, and resultant tachycardia (fast heart rate) and hypertrophiccardiomyopathy)

t presents before 25 years of age with progressive staggering or stumbling gait and frequent falling. Lowerextremities are more severely involved. The symptoms are slow and progressive. Long-term observation sho

hat many patients reach a plateau in symptoms in the patient's early adulthood. On average, after 1015 year

with the disease, patients are usually wheelchair bound and require assistance with all activities of daily

iving.[7]

The following physical signs may be detected on physical examination:

Cerebellar: Nystagmus, fast saccadic eye movements, truncal ataxia, dysarthria, dysmetria.
https://en.wikipedia.org/wiki/Dysmetriahttps://en.wikipedia.org/wiki/Dysarthriahttps://en.wikipedia.org/wiki/Saccadichttps://en.wikipedia.org/wiki/Nystagmushttps://en.wikipedia.org/wiki/Cerebellarhttps://en.wikipedia.org/wiki/Physical_examinationhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-7https://en.wikipedia.org/wiki/Activities_of_daily_livinghttps://en.wikipedia.org/wiki/Hypertrophic_cardiomyopathyhttps://en.wikipedia.org/wiki/Tachycardiahttps://en.wikipedia.org/wiki/Atrial_fibrillationhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-Diabetes-6https://en.wikipedia.org/wiki/Diabeteshttps://en.wikipedia.org/wiki/Pes_cavushttps://en.wikipedia.org/wiki/Plantar_archhttps://en.wikipedia.org/wiki/Scoliosishttps://en.wikipedia.org/wiki/Speechhttps://en.wikipedia.org/wiki/Hearing_impairmenthttps://en.wikipedia.org/wiki/Vision_impairmenthttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-5https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-4https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-3https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-2https://en.wikipedia.org/wiki/University_of_Heidelberghttps://en.wikipedia.org/wiki/Pathologyhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#External_linkshttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Referenceshttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#In_popular_culturehttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Epidemiologyhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#In_Researchhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Nicotinamidehttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#RG2833https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Idebenonehttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Treatmenthttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Pathogenesishttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Pathologyhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#Genetics


3/8



Friedreich's ataxia has an autosoma

recessive pattern of inheritance.

Lower motor neuron lesion: absent deep tendon reflexes.Pyramidal: 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 cardiomyopathysymmetrical hypertrophy, heart murmurs, and conduction defects. Median age of death is 35 years, whfemales have better prognosis with a 20-year survival of 100% as compared to 63% in men.

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

Genetics

Friedreich's ataxia is an autosomal recessive disorder that occurs when

he FXN gene contains amplified intronic GAA repeats (an example of

Trinucleotide repeat expansion). The FXN gene encodes the protein

frataxin.[8]GAA repeat expansion causes frataxin levels to be reduced.

Frataxin is an iron-binding protein responsible for forming ironsulphur

clusters. One result of frataxin deficiency is mitochondrial iron overload

which can cause damage to many proteins.[8]The exact role of frataxin

n normal physiology remains unclear.[9]The gene is located on

chromosome 9.

The mutant gene contains expanded GAA triplet repeats in the first

ntron;[10]in a few pedigrees, point mutations have been detected.

Because the defect is located in 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,

he mutation causes gene silencing (i.e., the mutation decreases theranscription of the gene) through induction of a heterochromatin

structure in a manner similar to position-effect variegation.[11]

Besides reducing expression of frataxin, long tracts of GAA repeats induce chromosome breaks in in vivoye

studies.

Pathology

The primary site of pathology is spinal cord and peripheral nerves. Sclerosis and degeneration of dorsal rootganglion, spinocerebellar tracts, Lateral corticospinal tracts, and posterior columns.[12]The motor neurons o

he spinal cord are spared. In peripheral nerves there is a loss of large myelinated fibres.

Progressive destruction of dorsal root ganglia accounts for thinning of dorsal roots, degeneration of dorsal

columns, transsynaptic atrophy of nerve cells in Clarke's column and dorsal spinocerebellar fibers, atrophy o

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 corticonuclea
https://en.wikipedia.org/wiki/Dentate_nucleushttps://en.wikipedia.org/wiki/Cuneate_nucleushttps://en.wikipedia.org/wiki/Gracile_nucleushttps://en.wikipedia.org/w/index.php?title=Dorsal_spinocerebellar_fiber&action=edit&redlink=1https://en.wikipedia.org/wiki/Dorsal_root_ganglionhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-Delatycki_M.2C_Williamson_R.2C_Forrest_S_2000_1.E2.80.938_As-12https://en.wikipedia.org/wiki/Lateral_corticospinal_tracthttps://en.wikipedia.org/wiki/Spinocerebellar_tractshttps://en.wikipedia.org/wiki/Degenerationhttps://en.wikipedia.org/wiki/Sclerosis_(medicine)https://en.wikipedia.org/wiki/Peripheral_nerveshttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-11https://en.wikipedia.org/wiki/Position-effect_variegationhttps://en.wikipedia.org/wiki/Heterochromatinhttps://en.wikipedia.org/wiki/Gene_silencinghttps://en.wikipedia.org/wiki/Translation_(genetics)https://en.wikipedia.org/wiki/Transcription_(genetics)https://en.wikipedia.org/wiki/Intronhttps://en.wikipedia.org/wiki/Point_mutationshttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-10https://en.wikipedia.org/wiki/Intronhttps://en.wikipedia.org/wiki/Trinucleotide_repeat_disordershttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-9https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-pmid21734495-8https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-pmid21734495-8https://en.wikipedia.org/wiki/Frataxinhttps://en.wikipedia.org/wiki/Trinucleotide_repeat_expansionhttps://en.wikipedia.org/wiki/Intronichttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-Diabetes-6https://en.wikipedia.org/wiki/Diabetes_mellitushttps://en.wikipedia.org/wiki/Heart_murmurshttps://en.wikipedia.org/wiki/Hypertrophyhttps://en.wikipedia.org/wiki/Cardiomyopathyhttps://en.wikipedia.org/wiki/Cardiomegalyhttps://en.wikipedia.org/wiki/Dorsal_columnhttps://en.wikipedia.org/wiki/Pyramid_(brainstem)https://en.wikipedia.org/wiki/Lower_motor_neuronhttps://en.wikipedia.org/wiki/File:Autorecessive.svg


4/8



synaptic terminals that contain gamma-aminobutyric acid (GABA). Small GABA-ergic neurons and their

projection fibers in the dentato-olivary tract survive. Atrophy of Betz cells and corticospinal tracts constitute

second lesion.

Pathogenesis

Low frataxin levels lead to insufficient biosynthesis of iron-sulfur clusters that are required for mitochondria

electron transport and assembly of functional aconitase and iron dysmetabolism of the entire cell. In normalndividuals, the FXN gene encodes frataxin, a mitochondrial matrix protein. This globular protein consists of

wo !helices and seven "strands and is highly conserved, occurring in all eukaryotes and some

prokaryotes.[13]Frataxin has a variety of known functions. Frataxin assists iron-sulfur protein synthesis in th

electron transport chain to ultimately generate adenosine triphosphate (ATP), the energy currency necessary

carry out metabolic functions in cells. Frataxin also regulates iron transfer in the mitochondria in order provi

a proper amount of reactive oxygen species (ROS) to maintain normal processes.[14]Without frataxin, the

energy in the mitochondria fails, and excess iron causes extra ROS to be created, leading to further cell

damage.[13][14]

Treatment

A person suffering from Friedreich's Ataxia may require some surgical interventions (mainly for the spine an

heart). Often, titanium screws and rods are 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 require

for mobility and independence. Other assistive technology, such as a standing frame, can help reduce the

secondary complications of prolonged use of a wheelchair. The goal of surgery is to keep the patient ambula

as long as possible.

n many cases, patients experience significant heart conditions as well. These conditions are much morereatable, and are often countered with ACE inhibitors such as enalapril or lisinopril and other heart medicati

such as digoxin.

Persons with Friedreichs ataxia may also benefit from a conservative treatment approach for the managemen

of symptoms. Health professionals educated in neurological conditions, such as physical therapists and

occupational therapists, can prescribe an exercise program tailored to maximize function and independence.

address the ataxic gait pattern and loss of proprioception typically seen in persons with Friedreichs ataxia,

physical therapists can use visual cueing during gait training to help facilitate a more efficient gait pattern. [15

The prescription of an assistive device along with gait training can also prolong independent ambulation. [15]

Low intensity strengthening exercises should also be incorporated to maintain functional use of the upper an

ower extremities.[16]Fatigability should be monitored closely. Stabilization exercises of the trunk and low b

can help with postural control and the management of scoliosis.[15]This is especially indicative if the person

non-ambulatory and requires the use of a wheelchair. Balance and coordination training using visual feedbac
https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-powers-15https://en.wikipedia.org/wiki/Scoliosishttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-mda-16https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-powers-15https://en.wikipedia.org/wiki/Gaithttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-powers-15https://en.wikipedia.org/wiki/Gaithttps://en.wikipedia.org/wiki/Gaithttps://en.wikipedia.org/wiki/Physical_therapistshttps://en.wikipedia.org/wiki/Proprioceptionhttps://en.wikipedia.org/wiki/Occupational_therapistshttps://en.wikipedia.org/wiki/Physical_therapistshttps://en.wikipedia.org/wiki/Digoxinhttps://en.wikipedia.org/wiki/ACE_inhibitorhttps://en.wikipedia.org/wiki/Wheelchairhttps://en.wikipedia.org/wiki/Standing_framehttps://en.wikipedia.org/wiki/Assistive_technologyhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-Sahdeo-14https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-Pandolfo-13https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-Sahdeo-14https://en.wikipedia.org/wiki/Iron-sulfur_proteinhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-Pandolfo-13https://en.wikipedia.org/wiki/Aconitasehttps://en.wikipedia.org/wiki/Corticospinal_tracthttps://en.wikipedia.org/wiki/Betz_cellhttps://en.wikipedia.org/w/index.php?title=Dentato-olivary_tract&action=edit&redlink=1https://en.wikipedia.org/wiki/Gamma-aminobutyric_acid


5/8



can also be incorporated into activities of daily living.[15]Exercises should reflect functional tasks such as

cooking, transfers and self-care. Along with gait training, balance and coordination training should be

developed to help minimize the risk of falls.[15]

Stretching exercises can be prescribed to help relieve tight musculature due to scoliosis and pes cavus

deformities.[16]

Idebenone

debenone, an antioxidant, was recently removed from the Canadian market in 2013 due to lack of

effectiveness. [17]

There is a Cochrane review on Antioxidants and other Pharmacological treatment in Friedreich Ataxia which

was published in 2012 and is due to be updated before the end of 2015. [18]

RG2833

RG2833 is a histone deacetylase inhibitor originally developed by Repligen but later acquired by BioMarin

Pharmaceutical in January 2014.[19]The first human trials with this compound began in 2012.[20]

Nicotinamide

Nicotinamide administration on patients was associated with a sustained improvement in frataxin concentrat

owards those seen in asymptomatic carriers during 8 weeks of daily dosing. The daily oral administration of

nicotinamide at the doage of 38 g would result in a 15-times increase and 75 g in a doubling of frataxin

protein concentration.[21]

Speech Therapy

Patients also often undertake speech therapy since dysarthria (a motor speech disorder) occurs in almost 100

of Friedreich's ataxia patients. Speech therapy seeks to improve speech outcomes and/or compensate for

communication deficits.[22]

In Research

Studies by Horizon Pharma on the use of interferon gamma-1B for treatment was recently given fast trackdesignation by the Food and Drug Administration. [23]

Epidemiology

Friedreich's ataxia is the most prevalent inherited ataxia,[24]affecting about 1 in 50,000 people in the United

States. Males and females are affected equally. The estimated carrier prevalence is 1:110.
https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-pmid16677089-24https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-23https://en.wikipedia.org/wiki/Food_and_Drug_Administrationhttps://en.wikipedia.org/wiki/Interferon_gammahttps://en.wikipedia.org/wiki/Horizon_Pharmahttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-22https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-21https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-trials-20https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-19https://en.wikipedia.org/wiki/BioMarin_Pharmaceuticalhttps://en.wikipedia.org/wiki/Repligenhttps://en.wikipedia.org/wiki/Histone_deacetylase_inhibitorhttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-18https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-17https://en.wikipedia.org/wiki/Idebenonehttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-mda-16https://en.wikipedia.org/wiki/Pes_cavushttps://en.wikipedia.org/wiki/Scoliosishttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-powers-15https://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-powers-15


6/8



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.[25]

In popular culture

The 2007 film The Cake Eatersstars Kristen Stewart as Georgia Kaminski, a teenager living with the condit

The 2003 book "The Great Fire (novel)" by Shirley Hazzard has Benedict, a teenager living with the conditio

References

1. synd/1406 (http://www.whonamedit.com/synd.cfm/1406.html)at Who Named It?

2. Friedreich N (1863). "Ueber degenerative Atrophie der spinalen Hinterstrnge" [About degenerative atrophy of the

spinal posterior column].Arch Pathol Anat Phys Klin Med(in German) 26(34): 391419. doi:10.1007/BF0193097

(https://dx.doi.org/10.1007%2FBF01930976).







5. Friedreich N (1876). "Ueber Ataxie mit besonderer Bercksichtigung der hereditren Formen" [About ataxia with

special reference to hereditary forms].Arch Pathol Anat Phys Klin Med(in German) 68(2): 145245.

doi:10.1007/BF01879049 (https://dx.doi.org/10.1007%2FBF01879049).

6. Thoren, Claes (June 1962). "Diabetes Mellitus in Friedreich's Ataxia".Acta Paediatrica51: 239247.

doi:10.1111/j.1651-2227.1962.tb08680.x (https://dx.doi.org/10.1111%2Fj.1651-2227.1962.tb08680.x). PMID 13921

(https://www.ncbi.nlm.nih.gov/pubmed/13921008).

7. Pandolfo M (2009). "Friedreich ataxia: The clinical picture".Journal of Neurology, 256:(1 Suppl), 3-8, doi:10.1007/s00415-009-1002-3

8. Klockgether T (August 2011). "Update on degenerative ataxias". Curr. Opin. Neurol.24(4): 33945.

doi:10.1097/WCO.0b013e32834875ba (https://dx.doi.org/10.1097%2FWCO.0b013e32834875ba). PMID 21734495


9. Marmolino, D. (2011). "Friedreich's ataxia: Past, present and future".Brain Research Reviews67(12): 311330.

doi:10.1016/j.brainresrev.2011.04.001 (https://dx.doi.org/10.1016%2Fj.brainresrev.2011.04.001). PMID 21550666


10. Montermini L, Andermann E, Labuda M et al. (August 1997). "The Friedreich ataxia GAA triplet repeat: premutatio

and normal alleles".Hum. Mol. Genet.6(8): 12616. doi:10.1093/hmg/6.8.1261

(https://dx.doi.org/10.1093%2Fhmg%2F6.8.1261). PMID 9259271 (https://www.ncbi.nlm.nih.gov/pubmed/9259271

11. Friedreich Ataxia (http://emedicine.medscape.com/article/1150420-overview)at eMedicine12. Delatycki M, Williamson R, Forrest S (2000). "Friedreich ataxia: an overview"

(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734457).J Med Genet37(1): 18 As. doi:10.1136/jmg.37.1.1

(https://dx.doi.org/10.1136%2Fjmg.37.1.1). PMC 1734457 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC173445

PMID 10633128 (https://www.ncbi.nlm.nih.gov/pubmed/10633128).

13. Pandolfo, M (October 2008). "Friedreich ataxia.".Archives of neurology65(10): 1296303.

doi:10.1001/archneur.65.10.1296 (https://dx.doi.org/10.1001%2Farchneur.65.10.1296). PMID 18852343

https://www.ncbi.nlm.nih.gov/pubmed/18852343https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1001%2Farchneur.65.10.1296https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/10633128https://en.wikipedia.org/wiki/PubMed_Identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734457https://en.wikipedia.org/wiki/PubMed_Centralhttps://dx.doi.org/10.1136%2Fjmg.37.1.1https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734457https://en.wikipedia.org/wiki/EMedicinehttp://emedicine.medscape.com/article/1150420-overviewhttps://www.ncbi.nlm.nih.gov/pubmed/9259271https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1093%2Fhmg%2F6.8.1261https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/21550666https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1016%2Fj.brainresrev.2011.04.001https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/21734495https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1097%2FWCO.0b013e32834875bahttps://en.wikipedia.org/wiki/Digital_object_identifierhttps://dx.doi.org/10.1007/s00415-009-1002-3https://www.ncbi.nlm.nih.gov/pubmed/13921008https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1111%2Fj.1651-2227.1962.tb08680.xhttps://en.wikipedia.org/wiki/Digital_object_identifierhttps://dx.doi.org/10.1007%2FBF01879049https://en.wikipedia.org/wiki/Digital_object_identifierhttps://dx.doi.org/10.1007%2FBF01938516https://en.wikipedia.org/wiki/Digital_object_identifierhttps://dx.doi.org/10.1007%2FBF01878006https://en.wikipedia.org/wiki/Digital_object_identifierhttps://dx.doi.org/10.1007%2FBF01930976https://en.wikipedia.org/wiki/Digital_object_identifierhttps://en.wikipedia.org/wiki/Who_Named_It%3Fhttp://www.whonamedit.com/synd.cfm/1406.htmlhttps://en.wikipedia.org/wiki/Shirley_Hazzardhttps://en.wikipedia.org/wiki/The_Great_Fire_(novel)https://en.wikipedia.org/wiki/Kristen_Stewarthttps://en.wikipedia.org/wiki/The_Cake_Eatershttps://en.wikipedia.org/wiki/Friedreich%27s_ataxia#cite_note-25https://en.wikipedia.org/wiki/Jean_Guyonhttps://en.wikipedia.org/wiki/New_Francehttps://en.wikipedia.org/wiki/French-Canadian


7/8



14. Sahdeo, S.; Scott, B. D.; McMackin, M. Z.; Jasoliya, M.; Brown, B.; Wulff, H.; Perlman, S. L.; Pook, M. A.; Cortop

G. A. (11 August 2014). "Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with

Friedreich's ataxia".Human Molecular Genetics23: 684862. doi:10.1093/hmg/ddu408

(https://dx.doi.org/10.1093%2Fhmg%2Fddu408). PMID 25113747 (https://www.ncbi.nlm.nih.gov/pubmed/2511374

15. Powers, Wendy (2007-01-01). "Holding Steady: How physical therapy can help patients with Friedreich's Ataxia"

(http://www.fortnet.org/fapg/PTarticleFA.htm). Advance18(1): 26. Retrieved 2011-05-16.

16. "Facts About Friedreich's Ataxia (FA)" (http://www.mdausa.org/publications/fa-fried-qa.html).Muscular Dystrophy

Association. 2011. Retrieved 2011-05-16.

17. "CATENA (idebenone) - Voluntary withdrawal of CATENA from the Canadian market - For the Public - Recalls & a- Healthy Canadians Website" (http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/23519a-eng.php).

Healthycanadians.gc.ca. Retrieved 2015-07-04.

18. Kearney, Mary; Orrell, Richard W; Fahey, Michael; Pandolfo, Massimo; Kearney, Mary (2012). "Antioxidants and o

pharmacological treatments for Friedreich ataxia". The Cochrane Database of Systematic Reviews4: CD007791.

doi:10.1002/14651858.CD007791.pub3 (https://dx.doi.org/10.1002%2F14651858.CD007791.pub3). PMID 2251395


19. "BioMarin Announces Agreement With Repligen for Pre-clinical Compounds (NASDAQ:BMRN)"

(http://investors.bmrn.com/releasedetail.cfm?ReleaseID=820213). Investors.bmrn.com. 2014-01-21. Retrieved

2015-07-04.

20. "FARA Human Trials" (http://www.curefa.org/_pdf/PressRelease03-15-12.pdf) (PDF). Friedreich's Ataxia Research

Alliance. 2012. Retrieved 2012-03-15.

21. Libri, Vincenzo; Yandim, Cihangir; Athanasopoulos, Stavros; Loyse, Naomi; Natisvili, Theona; Law, Pui Pik; Chan,

Ping Kei; Mohammad, Tariq; Mauri, Marta; Tam, Kin Tung; Leiper, James; Piper, Sophie; Ramesh, Aravind; Parkin

Michael H; Huson, Les; Giunti, Paola; Festenstein, Richard (2014). "Epigenetic and neurological effects and safety o

high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study". The

Lancet384(9942): 50413. doi:10.1016/S0140-6736(14)60382-2 (https://dx.doi.org/10.1016%2FS0140-

6736%2814%2960382-2). PMID 24794816 (https://www.ncbi.nlm.nih.gov/pubmed/24794816).

22. Vogel, Adam P; Folker, Joanne; Poole, Matthew L; Vogel, Adam P (2014). "Treatment for speech disorder in Friedre

ataxia and other hereditary ataxia syndromes". The Cochrane Database of Systematic Reviews10: CD008953.

doi:10.1002/14651858.CD008953.pub2 (https://dx.doi.org/10.1002%2F14651858.CD008953.pub2). PMID 2534858


23. Dulaney, Chelsey (2015-04-10). "Horizon Pharmas Friedreichs Ataxia Drug Gets Fast-Track Designation"

(http://www.wsj.com/articles/horizon-pharmas-friedreichs-ataxia-drug-gets-fast-track-designation-1428665791). WSRetrieved 2015-07-04.

24. Lodi R, Tonon C, Calabrese V, Schapira AH (2006). "Friedreich's ataxia: from disease mechanisms to therapeutic

interventions".Antioxid. Redox Signal.8(34): 43843. doi:10.1089/ars.2006.8.438

(https://dx.doi.org/10.1089%2Fars.2006.8.438). PMID 16677089 (https://www.ncbi.nlm.nih.gov/pubmed/16677089)

25. 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 neurologiques11(4 Supp

5069. PMID 6391645 (https://www.ncbi.nlm.nih.gov/pubmed/6391645).

External links

European Friedreich's Ataxia Consortium for Translational Studies (http://www.e-facts.eu/)friedreichs_ataxia (http://www.ninds.nih.gov/disorders/friedreichs_ataxia)at NINDSfriedreich (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=friedreich)at NIH/UWGeneTestsFARA The Friedreich's Ataxia Research Alliance (http://curefa.org/index.html) at www.cureFA.orgAsks the Experts - Responses: Friedreich's Ataxia (http://www.mdausa.org/experts/responses.cfm?id=at Muscular Dystrophy AssociationNCBI Genes and Disease: Friedreich's ataxia (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.205https://en.wikipedia.org/wiki/Muscular_Dystrophy_Associationhttp://www.mdausa.org/experts/responses.cfm?id=92http://curefa.org/index.htmlhttps://en.wikipedia.org/wiki/University_of_Washingtonhttps://en.wikipedia.org/wiki/National_Institutes_of_Healthhttp://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=friedreichhttps://en.wikipedia.org/wiki/National_Institute_of_Neurological_Disorders_and_Strokehttp://www.ninds.nih.gov/disorders/friedreichs_ataxiahttp://www.e-facts.eu/https://www.ncbi.nlm.nih.gov/pubmed/6391645https://en.wikipedia.org/wiki/PubMed_Identifierhttps://www.ncbi.nlm.nih.gov/pubmed/16677089https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1089%2Fars.2006.8.438https://en.wikipedia.org/wiki/Digital_object_identifierhttp://www.wsj.com/articles/horizon-pharmas-friedreichs-ataxia-drug-gets-fast-track-designation-1428665791https://www.ncbi.nlm.nih.gov/pubmed/25348587https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1002%2F14651858.CD008953.pub2https://en.wikipedia.org/wiki/Digital_object_identifierhttps://www.ncbi.nlm.nih.gov/pubmed/24794816https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1016%2FS0140-6736%2814%2960382-2https://en.wikipedia.org/wiki/Digital_object_identifierhttp://www.curefa.org/_pdf/PressRelease03-15-12.pdfhttp://investors.bmrn.com/releasedetail.cfm?ReleaseID=820213https://www.ncbi.nlm.nih.gov/pubmed/22513953https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1002%2F14651858.CD007791.pub3https://en.wikipedia.org/wiki/Digital_object_identifierhttp://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2013/23519a-eng.phphttp://www.mdausa.org/publications/fa-fried-qa.htmlhttp://www.fortnet.org/fapg/PTarticleFA.htmhttps://www.ncbi.nlm.nih.gov/pubmed/25113747https://en.wikipedia.org/wiki/PubMed_Identifierhttps://dx.doi.org/10.1093%2Fhmg%2Fddu408https://en.wikipedia.org/wiki/Digital_object_identifier


8/8



rid=gnd.section.205) at National Center for Biotechnology InformationCanadian Association for Familial Ataxias - Claude St-Jean Foundation (http://www.lacaf.org/index.poption=com_frontpage&Itemid=1&lang=english)British Columbia (BC) Ataxia Society (http://www.bcataxia.org/)

Retrieved from "https://en.wikipedia.org/w/index.php?title=Friedreich%27s_ataxia&oldid=669957367"

Categories: Systemic atrophies primarily affecting the central nervous system Autosomal recessive disordeMitochondrial diseases Trinucleotide repeat disorders

This page was last modified on 4 July 2015, at 19:58.Text is available under the Creative Commons Attribution-ShareAlike License; additional terms mayapply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia is a registeredtrademark of the Wikimedia Foundation, Inc., a non-profit organization.
https://www.wikimediafoundation.org/https://wikimediafoundation.org/wiki/Privacy_policyhttps://wikimediafoundation.org/wiki/Terms_of_Usehttps://en.wikipedia.org/wiki/Wikipedia:Text_of_Creative_Commons_Attribution-ShareAlike_3.0_Unported_Licensehttps://en.wikipedia.org/wiki/Help:Categoryhttps://en.wikipedia.org/w/index.php?title=Friedreich%27s_ataxia&oldid=669957367http://www.bcataxia.org/http://www.lacaf.org/index.php?option=com_frontpage&Itemid=1&lang=englishhttps://en.wikipedia.org/wiki/National_Center_for_Biotechnology_Informationhttp://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.205https://en.wikipedia.org/wiki/Category:Trinucleotide_repeat_disordershttps://en.wikipedia.org/wiki/Category:Mitochondrial_diseaseshttps://en.wikipedia.org/wiki/Category:Autosomal_recessive_disordershttps://en.wikipedia.org/wiki/Category:Systemic_atrophies_primarily_affecting_the_central_nervous_system

wikipedia - friedreich's ataxia (checked).pdf

Documents