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FRDA
MCID: FRD001
MIFTS: 64

Friedreich Ataxia (FRDA)

Categories: Cardiovascular diseases, Eye diseases, Genetic diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
Sources

Aliases & Classifications for Friedreich Ataxia

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MalaCards integrated aliases for Friedreich Ataxia:

Name: Friedreich Ataxia 56 12 24 52 25 53 58 73 36 54 43 15 39
Friedreich Ataxia 1 56 12 73 29 6 15
Friedreich's Ataxia 12 74 52 29 6 42
Frda 56 24 52 25 58 73
Friedreich Ataxia with Retained Reflexes 56 73 29 13 6
Frda1 56 12 73 54
Fa 56 25 58 73
Spinocerebellar Ataxia, Friedreich 52
Friedreich Spinocerebellar Ataxia 25
Hereditary Spinal Sclerosis 52
Friedreich Ataxia 1; Frda1 56
Friedreich Ataxia, Type 1 39
Hereditary Spinal Ataxia 52
Friedreich's Tabes 12
Friedrich's Ataxia 25
Fa1 12

Characteristics:

Orphanet epidemiological data:

58
friedreich ataxia
Inheritance: Autosomal recessive; Prevalence: 1-9/100000 (Europe),1-9/100000 (France),1-9/100000 (Italy),1-9/1000000 (Finland); Age of onset: Adolescent,Childhood; Age of death: adult;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset before adolescence
most common inherited ataxia
estimated carrier frequency 1/100
patients often nonambulatory by the mid-twenties
major cause of death is heart failure
average age at death is 37 years
most common genetic abnormality is a (gaa)n trinucleotide repeat expansion in intron 1 of the fxn gene
repeat expansions range from 70 to over 1,000 (normal 5 to 30 repeats)


HPO:

31
friedreich ataxia:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset


GeneReviews:

24
Penetrance Penetrance is complete in those with biallelic full-penetrance gaa repeat expansions and in compound heterozygotes for a full-penetrance gaa expansion in one allele and a fxn pathogenic variant in the other allele. however, because of wide variability in the size of pathogenic expanded alleles, and for other unknown reasons, onset can range from before age five years to after age 50 years. this variability in age-dependent penetrance can occasionally occur within the same sibship....

Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Neuronal diseases Eye diseases Cardiovascular diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare neurological diseases
Rare eye diseases


Sources

Summaries for Friedreich Ataxia

About this section
Genetics Home Reference : 25 Friedreich ataxia is a genetic condition that affects the nervous system and causes movement problems. People with this condition develop impaired muscle coordination (ataxia) that worsens over time. Other features of this condition include the gradual loss of strength and sensation in the arms and legs; muscle stiffness (spasticity); and impaired speech, hearing, and vision. Individuals with Friedreich ataxia often have a form of heart disease called hypertrophic cardiomyopathy, which enlarges and weakens the heart muscle and can be life-threatening. Some affected individuals develop diabetes or an abnormal curvature of the spine (scoliosis). Most people with Friedreich ataxia begin to experience the signs and symptoms of the disorder between ages 5 and 15. Poor coordination and balance are often the first noticeable features. Affected individuals typically require the use of a wheelchair about 10 years after signs and symptoms appear. About 25 percent of people with Friedreich ataxia have an atypical form in which signs and symptoms begin after age 25. Affected individuals who develop Friedreich ataxia between ages 26 and 39 are considered to have late-onset Friedreich ataxia (LOFA). When the signs and symptoms begin after age 40 the condition is called very late-onset Friedreich ataxia (VLOFA). LOFA and VLOFA usually progress more slowly than typical Friedreich ataxia.

MalaCards based summary : Friedreich Ataxia, also known as friedreich ataxia 1, is related to friedreich ataxia 2 and vitamin e, familial isolated deficiency of, and has symptoms including seizures, ataxia and myoclonus. An important gene associated with Friedreich Ataxia is FXN (Frataxin), and among its related pathways/superpathways are Spinocerebellar ataxia and Iron metabolism in placenta. The drugs Citalopram and Bupropion have been mentioned in the context of this disorder. Affiliated tissues include heart, brain and spinal cord, and related phenotypes are gait ataxia and dysarthria

NIH Rare Diseases : 52 Friedreich ataxia is an inherited condition that affects the nervous system and causes movement problems. People with this condition develop impaired muscle coordination (ataxia) that worsens over time. Other features include the gradual loss of strength and sensation in the arms and legs, muscle stiffness (spasticity ), and impaired speech. Many individuals have a form of heart disease called hypertrophic cardiomyopathy . Some develop diabetes, impaired vision, hearing loss , or an abnormal curvature of the spine (scoliosis ). Most people with Friedreich ataxia begin to experience the signs and symptoms around puberty. This condition is caused by mutations in the FXN gene and is inherited in an autosomal recessive pattern.

OMIM : 56 Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia with associated limb muscle weakness, absent lower limb reflexes, extensor plantar responses, dysarthria, and decreased vibratory sense and proprioception. Onset is usually in the first or second decade, before the end of puberty. It is one of the most common forms of autosomal recessive ataxia, occurring in about 1 in 50,000 individuals. Other variable features include visual defects, scoliosis, pes cavus, and cardiomyopathy (review by Delatycki et al., 2000). Pandolfo (2008) provided an overview of Friedreich ataxia, including pathogenesis, mutation mechanisms, and genotype/phenotype correlation. (229300)

MedlinePlus : 42 Friedreich's ataxia is an inherited disease that damages your nervous system. The damage affects your spinal cord and the nerves that control muscle movement in your arms and legs. Symptoms usually begin between the ages of 5 and 15. The main symptom is ataxia, which means trouble coordinating movements. Specific symptoms include Difficulty walking Muscle weakness Speech problems Involuntary eye movements Scoliosis (curving of the spine to one side) Heart palpitations, from the heart disease which can happen along with Friedreich's ataxia People with Friedreich's ataxia usually need a wheelchair 15 to 20 years after symptoms first appear. In severe cases, people become incapacitated. There is no cure. You can treat symptoms with medicines, braces, surgery, and physical therapy. NIH: National Institute of Neurological Disorders and Stroke

NINDS : 53 Friedreich ataxia is a rare inherited disease that causes progressive damage to the nervous system. It is caused by a defect in the FXN gene that produces the protein frataxin. Frataxin controls important steps in mitochondrial iron metabolism and overall cell iron stability. Research suggests that cells that have a reduced level of frataxin produce energy less effectively, which may lead to a buildup of toxic byproducts. Symptoms typically appear between ages 5 and 15 years but can begin in adulthood. Damage to the peripheral nerves and the cerebellum (part of the brain that coordinates balance and movement) results in awkward, unsteady movements and impaired muscle coordination (ataxia) that worsens and eventually spreads to the arms and the trunk of the body. Other symptoms include loss of sensory function, speech problems, and vision and hearing loss. Thinking and reasoning abilities are not affected. Many people with Friedreich ataxia develop scoliosis (a curving of the spine to one side), which, if severe, may impair breathing. Some individuals may develop diabetes.

KEGG : 36 Friedreich ataxia is one of the most common forms of autosomal recessive ataxia caused by severely reduced levels of frataxin as a result of a large GAA triplet-repeat expansion within the first intron of the frataxin gene. Frataxin deficiency is thought to cause generation of reactive oxygen species, reactive nitrogen species and mitochondrial dysfunction.

UniProtKB/Swiss-Prot : 73 Friedreich ataxia: Autosomal recessive, progressive degenerative disease characterized by neurodegeneration and cardiomyopathy it is the most common inherited ataxia. The disorder is usually manifest before adolescence and is generally characterized by incoordination of limb movements, dysarthria, nystagmus, diminished or absent tendon reflexes, Babinski sign, impairment of position and vibratory senses, scoliosis, pes cavus, and hammer toe. In most patients, FRDA is due to GAA triplet repeat expansions in the first intron of the frataxin gene. But in some cases the disease is due to mutations in the coding region.

Wikipedia : 74 Friedreich's ataxia (FRDA or FA) is an autosomal recessive genetic disease that causes difficulty... more...

GeneReviews: NBK1281
Sources

Related Diseases for Friedreich Ataxia

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Diseases in the Friedreich Ataxia family:

Friedreich Ataxia 2

Diseases related to Friedreich Ataxia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 1240)
# Related Disease Score Top Affiliating Genes
1 friedreich ataxia 2 35.2 PIP5K1B FXN FTMT FRDA2
2 vitamin e, familial isolated deficiency of 33.2 TTPA SETX FXN APTX
3 anemia, sideroblastic, and spinocerebellar ataxia 33.1 FXN ACO1
4 ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia 32.7 TTPA SETX FXN CACNA1A APTX
5 spastic ataxia, charlevoix-saguenay type 32.5 TTPA SETX FXN APTX
6 mitochondrial dna depletion syndrome 7 32.2 FXN APTX
7 atrial standstill 1 31.9 MIPEP HFE FXN
8 hemosiderosis 31.7 TFRC HFE FXN ACO1
9 tremor 31.2 FMR1 CACNA1A ATXN2
10 hereditary ataxia 31.2 TTPA SETX FXN CACNA1A ATXN8OS ATXN2
11 tabes dorsalis 31.1 TTPA FXN
12 machado-joseph disease 31.0 CACNA1A ATXN8OS ATXN2
13 primary cerebellar degeneration 30.9 CACNA1A ATXN2
14 hemochromatosis, type 1 30.9 TFRC SETX HFE FXN ATXN2 ACO1
15 spinocerebellar ataxia 36 30.9 ATXN8OS ATXN2
16 spinocerebellar ataxia 1 30.9 FXN FMR1 CACNA1A ATXN8OS ATXN2
17 iron metabolism disease 30.8 TFRC HFE ACO1
18 restless legs syndrome 30.7 TFRC FTMT FMR1 CACNA1A ATXN2 ACO1
19 autosomal dominant cerebellar ataxia 30.6 TTPA SETX FXN FMR1 CACNA1A ATXN8OS
20 spinocerebellar ataxia 6 30.6 FXN CACNA1A ATXN8OS ATXN2
21 cerebellar disease 30.6 TTPA SETX FXN FMR1 CACNA1A ATXN2
22 peripheral nervous system disease 30.5 SETX FXN CACNA1A APTX
23 spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 30.5 TTPA SETX FXN CACNA1A APTX
24 autosomal recessive cerebellar ataxia 30.2 TTPA SETX LYRM4 FXN FANCB EPPIN
25 sideroblastic anemia 30.0 TFRC HFE FXN FTMT ACO1
26 friedreich ataxia and congenital glaucoma 12.4
27 fanconi anemia, complementation group a 12.4
28 friedreich ataxia, so-called, with optic atrophy and sensorineural deafness 12.3
29 charcot-marie-tooth peroneal muscular atrophy and friedreich ataxia, combined 12.3
30 autoimmune lymphoproliferative syndrome 12.1
31 fetal alcohol syndrome 12.1
32 ataxia with vitamin e deficiency 11.7
33 mycosis fungoides 11.6
34 cerebellar ataxia, early-onset, with retained tendon reflexes 11.6
35 auditory neuropathy, autosomal dominant, 1 11.6
36 graft-versus-host disease 11.6
37 fanconi anemia, complementation group d2 11.6
38 fanconi anemia, complementation group i 11.6
39 fetal alcohol spectrum disorder 11.6
40 fanconi anemia, complementation group l 11.6
41 fanconi anemia, complementation group j 11.5
42 fanconi anemia, complementation group d1 11.5
43 fanconi anemia, complementation group n 11.5
44 fanconi anemia, complementation group b 11.5
45 fanconi anemia, complementation group o 11.5
46 dianzani autoimmune lymphoproliferative disease 11.5
47 adult t-cell leukemia 11.4
48 ataxia and polyneuropathy, adult-onset 11.4
49 fanconi anemia, complementation group c 11.4
50 sperm-specific antigen 1 11.4

Graphical network of the top 20 diseases related to Friedreich Ataxia:



Diseases related to Friedreich Ataxia
Sources

Symptoms & Phenotypes for Friedreich Ataxia

About this section

Human phenotypes related to Friedreich Ataxia:

58 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 gait ataxia 58 31 obligate (100%) Obligate (100%) HP:0002066
2 dysarthria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001260
3 gait imbalance 58 31 hallmark (90%) Very frequent (99-80%) HP:0002141
4 babinski sign 58 31 hallmark (90%) Very frequent (99-80%) HP:0003487
5 impaired proprioception 58 31 hallmark (90%) Very frequent (99-80%) HP:0010831
6 limb ataxia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002070
7 hand muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009130
8 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
9 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
10 muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0001324
11 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
12 dysmetria 58 31 frequent (33%) Frequent (79-30%) HP:0001310
13 pes cavus 58 31 frequent (33%) Frequent (79-30%) HP:0001761
14 cardiomyopathy 58 31 frequent (33%) Frequent (79-30%) HP:0001638
15 intention tremor 58 31 frequent (33%) Frequent (79-30%) HP:0002080
16 poor fine motor coordination 58 31 frequent (33%) Frequent (79-30%) HP:0007010
17 urinary bladder sphincter dysfunction 58 31 frequent (33%) Frequent (79-30%) HP:0002839
18 sensory axonal neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0003390
19 falls 58 31 frequent (33%) Frequent (79-30%) HP:0002527
20 areflexia of lower limbs 58 31 frequent (33%) Frequent (79-30%) HP:0002522
21 cervical spinal cord atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0010873
22 impaired visually enhanced vestibulo-ocular reflex 58 31 frequent (33%) Frequent (79-30%) HP:0030183
23 abnormal saccadic eye movements 31 frequent (33%) HP:0000570
24 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
25 spasticity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001257
26 dysphagia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002015
27 diabetes mellitus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000819
28 reduced visual acuity 58 31 occasional (7.5%) Occasional (29-5%) HP:0007663
29 dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001332
30 chorea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002072
31 decreased motor nerve conduction velocity 58 31 occasional (7.5%) Occasional (29-5%) HP:0003431
32 inability to walk 58 31 occasional (7.5%) Occasional (29-5%) HP:0002540
33 incomprehensible speech 58 31 occasional (7.5%) Occasional (29-5%) HP:0002546
34 abnormality of visual evoked potentials 31 HP:0000649
35 hypertrophic cardiomyopathy 31 HP:0001639
36 sensory neuropathy 31 HP:0000763
37 congestive heart failure 31 HP:0001635
38 abnormality of the foot 58 Frequent (79-30%)
39 impaired vibratory sensation 31 HP:0002495
40 visual field defect 31 HP:0001123
41 abnormality of saccadic eye movements 58 Frequent (79-30%)
42 abnormal ekg 31 HP:0003115
43 abnormal echocardiogram 31 HP:0003116
44 decreased amplitude of sensory action potentials 31 HP:0007078
45 decreased sensory nerve conduction velocity 31 HP:0003448
46 decreased pyruvate carboxylase activity 31 HP:0003209
47 mitochondrial malic enzyme reduced 31 HP:0003232

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Cardiovascular Heart:
hypertrophic cardiomyopathy

Endocrine Features:
diabetes mellitus

Laboratory Abnormalities:
abnormal ekg
abnormal echocardiogram
abnormal spinocerebellar tracts, dorsal columns, pyramidal tracts, cerebellum and brainstem
low pyruvate carboxylase activity in liver and cultured fibroblasts
decreased mitochondrial malic enzyme

Head And Neck Eyes:
optic atrophy
nystagmus
visual field defects
reduced visual acuity (less common)
reduced retinal nerve fiber layer thickness
more
Neurologic Central Nervous System:
nystagmus
dysarthria
impaired proprioception
gait and limb ataxia
impaired vibratory sense

Skeletal Feet:
pes cavus

Neurologic Peripheral Nervous System:
extensor plantar responses
peripheral sensory neuropathy
abnormal motor and sensory nerve conduction
absent lower limb tendon reflexes

Clinical features from OMIM:

229300

UMLS symptoms related to Friedreich Ataxia:


seizures, ataxia, myoclonus, tremor, back pain, headache, syncope, pain, chronic pain, sciatica, vertigo/dizziness, sleeplessness, cerebellar ataxia/dyskinesia

MGI Mouse Phenotypes related to Friedreich Ataxia:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.4 ACO1 APTX ATXN2 CACNA1A FANCB FXN
Sources

Drugs & Therapeutics for Friedreich Ataxia

About this section

Drugs for Friedreich Ataxia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 120)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Citalopram Approved Phase 4 59729-33-8 2771
2
Bupropion Approved Phase 4 34911-55-2, 34841-39-9 444
3
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
4 Cholinergic Agents Phase 4
5 Neurotransmitter Agents Phase 4
6 Dopamine Agents Phase 4
7 Cytochrome P-450 Enzyme Inhibitors Phase 4
8 Antidepressive Agents Phase 4
9 Parasympatholytics Phase 4
10 Antiparkinson Agents Phase 4
11 Psychotropic Drugs Phase 4
12 Serotonin Uptake Inhibitors Phase 4
13 Muscarinic Antagonists Phase 4
14 Cholinergic Antagonists Phase 4
15
Serotonin Investigational, Nutraceutical Phase 4 50-67-9 5202
16
Acetylcysteine Approved, Investigational Phase 2, Phase 3 616-91-1 12035
17
Metformin Approved Phase 2, Phase 3 657-24-9 14219 4091
18
Idebenone Approved, Investigational Phase 3 58186-27-9
19
Deferiprone Approved Phase 2, Phase 3 30652-11-0 2972
20
Iron Approved, Experimental Phase 2, Phase 3 15438-31-0, 7439-89-6 27284 23925
21
Riluzole Approved, Investigational Phase 2, Phase 3 1744-22-5 5070
22
Pioglitazone Approved, Investigational Phase 3 111025-46-8 4829
23
Varenicline Approved, Investigational Phase 2, Phase 3 249296-44-4 5310966
24
Coenzyme Q10 Approved, Investigational, Nutraceutical Phase 3 303-98-0 5281915
25 Hormones Phase 2, Phase 3
26 Hormone Antagonists Phase 2, Phase 3
27 Respiratory System Agents Phase 2, Phase 3
28 Antidotes Phase 2, Phase 3
29 Dipeptidyl-Peptidase IV Inhibitors Phase 2, Phase 3
30
protease inhibitors Phase 2, Phase 3
31 HIV Protease Inhibitors Phase 2, Phase 3
32 Sitagliptin Phosphate Phase 2, Phase 3
33 Incretins Phase 2, Phase 3
34 Expectorants Phase 2, Phase 3
35 N-monoacetylcystine Phase 2, Phase 3
36 Ubiquinone Phase 3
37 Antioxidants Phase 3
38 Protective Agents Phase 3
39 interferons Phase 3
40 Interferon-gamma Phase 3
41 Pharmaceutical Solutions Phase 2, Phase 3
42 Chelating Agents Phase 2, Phase 3
43 Iron Chelating Agents Phase 2, Phase 3
44 Neuroprotective Agents Phase 2, Phase 3
45 Excitatory Amino Acid Antagonists Phase 2, Phase 3
46 Anticonvulsants Phase 2, Phase 3
47 Hypoglycemic Agents Phase 3
48 Linoleate Phase 3
49 Nicotinic Agonists Phase 2, Phase 3
50
Tocopherol Approved, Investigational Phase 2 1406-66-2, 54-28-4 14986

Interventional clinical trials:

(show top 50) (show all 77)
# Name Status NCT ID Phase Drugs
1 An Objective Double-blind Evaluation of Bupropion and Citalopram in an Individual With Friedreich Ataxia Completed NCT01716221 Phase 4 bupropion & Citalopram;Bupropion & Placebo;Placebo & Citalopram;Placebo & Placebo
2 Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone, and Incretin Based Therapy Unknown status NCT02882477 Phase 2, Phase 3 Deferiprone;Acetylcysteine;Sitagliptin and Metformin
3 A Phase III Open-Label, Single-Group, Extension Study to Obtain Long-Term Safety and Tolerability Data of Idebenone in the Treatment of Friedreich's Ataxia Patients. Completed NCT00993967 Phase 3 idebenone
4 A Phase III Double-blind, Randomised, Placebo-controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients Completed NCT00905268 Phase 3 idebenone;Placebo
5 A Phase III Open-Label, Single Group Extension Study of the Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients Completed NCT00697073 Phase 3 Idebenone
6 A Phase III Double-Blind, Randomized, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in the Treatment of Friedreich's Ataxia Patients Completed NCT00537680 Phase 3 Idebenone;Idebenone;Placebo
7 A Phase IIIb Double-Blind, Randomised, Placebo-Controlled Study of Patient Reported Outcomes in Friedreich's Ataxia Patients After Withdrawal From Treatment With Idebenone Completed NCT01303406 Phase 3 Idebenone;Placebo
8 Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy, Safety, and Pharmacokinetic Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia Completed NCT02415127 Phase 3 Interferon γ-1b;Placebo
9 Efficacy of Riluzole in Hereditary Cerebellar Ataxia: a Randomized Double-blind Placebo-controlled Trial. Completed NCT01104649 Phase 2, Phase 3 riluzole;Placebo comparator
10 Multicenter, Safety and Efficacy, Open-Label Extension Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia Completed NCT02593773 Phase 3 Interferon γ-1b
11 Long-Term Safety Extension Study of ACTIMMUNE® (Interferon γ-1b) in Children and Young Adults With Friedreich's Ataxia Completed NCT02797080 Phase 3 interferon γ-1b
12 Effect of Pioglitazone Administered to Patients With Friedreich's ATAXIA:Proof of Concept Completed NCT00811681 Phase 3 pioglitazone;Placebo
13 Efficacy and Safety of the Iron Chelator Deferiprone on Iron Overload in the Brain in Parkinson's Disease Completed NCT00943748 Phase 2, Phase 3 deferiprone;placebo
14 A Randomized, Double-Blind, Controlled, Phase 2/3 Study to Assess Efficacy, Long Term Safety and Tolerability of RT001 in Subjects With Friedreich's Ataxia Recruiting NCT04102501 Phase 3 RT001;Placebo
15 Pilot Study of Varenicline (Chantix®) in the Treatment of Friedreich's Ataxia Terminated NCT00803868 Phase 2, Phase 3 varenicline;placebo
16 Pharmacodynamic Studies of a Histone Deacetylase Inhibitor in Friedreich's Ataxia Unknown status NCT01589809 Phase 2 nicotinamide
17 Safety and Efficacy Study of EPI-743 on Visual Function in Patients With Friedreich's Ataxia Completed NCT01728064 Phase 2 Placebo;EPI-743 400 mg;EPI-743 200 mg
18 A Phase IIa Clinical Trial to Test the Safety and Efficacy of Interferon Gamma Treatment in Elevating Frataxin Levels in Friedreich's Ataxia (FRDA) Patients Completed NCT02035020 Phase 2 gamma interferon
19 A Six-month Double-blind, Randomized, Placebo-controlled Study Investigating the Safety and Tolerability of Deferiprone in Patients With Friedreich's Ataxia Completed NCT00530127 Phase 1, Phase 2 placebo;deferiprone;deferiprone;placebo;deferiprone
20 An Open-label, Single Treatment, Safety and Efficacy, Long-term Study of Deferiprone in Subjects With Friedreich's Ataxia Completed NCT00897221 Phase 2 Deferiprone oral solution 100mg/mL;Deferiprone oral solution 100 mg/mL
21 Randomised, Double Blind, Placebo Controlled Study of Lu AA24493 in Patients With Friedreich's Ataxia to Evaluate Safety and Tolerability and to Explore Efficacy Completed NCT01016366 Phase 2 Lu AA24493;Placebo
22 A Double-blind, Randomized, Placebo-controlled, Clinical Trial to Test the Efficacy of Epoetin Alfa on Physical Performance of Friedreich Ataxia Patients. Completed NCT01493973 Phase 2 Epoetin alfa;Placebo
23 Single-Center, Open-Label, Sequential Trial to Test the Efficacy, Safety and Tolerability of Epoetin Alfa in Patients With Friedreich's Ataxia Completed NCT00631202 Phase 2 Epoetin alfa
24 A Phase II, Open Label Prospective Single Center Drug Study Evaluating the Safety and Efficacy of (+)-Epicatechin in Subjects With Friedreich's Ataxia Completed NCT02660112 Phase 2 (+)-Epicatechin
25 A Phase 2A Clinical Trial of EPI-743 (Vincerinone™) on Visual Function in Friedreich's Ataxia Patients With Point Mutations Completed NCT01962363 Phase 2 EPI-743
26 A Randomized, Double-blind, Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of RT001 in Patients With Friedreich's Ataxia Completed NCT02445794 Phase 1, Phase 2 RT001;RT001 comparator
27 Safety and Efficacy of γIFN Treatment in Friedreich Ataxia Completed NCT03888664 Phase 2 gamma interferon
28 Open-label Pilot Study of Interferon Gamma-1b (Actimmune™) for the Treatment of Friedreich Ataxia (FRDA) Completed NCT01965327 Phase 2 Interferon Gamma-1b
29 A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, 28 Day, Three-arm, Parallel Group Study of A0001 in the Treatment of Subjects With Friedreich's Ataxia Completed NCT01035671 Phase 2 alpha-tocopherolquinone (A0001);alpha-tocopherolquinone (A0001);placebo
30 A Six Month Double-Blind, Placebo-Controlled Phase 2 Clinical Trial to Determine the Safety and Efficacy of Idebenone Administered to Patients With Friedreich's Ataxia Completed NCT00229632 Phase 2 Idebenone
31 Efficacy of EGb761 120mg Bid Versus Placebo in Patients Suffering From Friedreich Ataxia. A 3 Month, Phase II, Randomised, Double Blind, Placebo Controlled, Parallel Group Clinical Study. Completed NCT00824512 Phase 2 EGb 761 120 mg;Placebo
32 An Open Label Clinical Pilot Study of Resveratrol as Treatment for Friedreich Ataxia Completed NCT01339884 Phase 1, Phase 2 Resveratrol
33 Effect of Iron-Chelating Therapy in Friedreich Ataxia. Study Phase I/II Completed NCT00224640 Phase 1, Phase 2 Iron chelating intervention
34 A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm Study to Evaluate Efficacy, Tolerability, and Pharmacokinetics of Multiple Doses of Oral TAK-831 in Adult Subjects With Friedreich Ataxia Completed NCT03214588 Phase 2 TAK-831;TAK-831 Placebo
35 A Phase IIa Double-Blind, Randomized, Placebo-Controlled, Dose-Finding Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-like Episodes Completed NCT00887562 Phase 2 Idebenone;Idebenone
36 A Pilot Clinical Trial With the Iron Chelator Deferiprone in Parkinson's Disease Completed NCT01539837 Phase 2 Deferiprone 20mg;Placebo;Deferiprone 30mg
37 A Randomized, Double-blind Multicenter Pilot Study vs. Placebo for the Evaluation of Efficacy and Tolerability of Tauroursodeoxycholic Acid Administered by Oral Route as Add on Treatment in Patients Affected by Amyotrophic Lateral Sclerosis Completed NCT00877604 Phase 2 tauroursodeoxycholic acid (TUDCA);Placebo
38 Long-Term Use of Inhaled Sodium Pyruvate for the Treatment of Chronic Obstructive Pulmonary Disease Completed NCT00262613 Phase 2 sodium pyruvate in 0.9% sodium chloride solution
39 Double Blind Placebo-Controlled Phase I/II Clinical Trial of Idebenone in Patients With Primary Progressive Multiple Sclerosis Completed NCT00950248 Phase 1, Phase 2 Idebenone
40 A Randomised Placebo-controlled Crossover Trial of Micronised Resveratrol as a Treatment for Friedreich Ataxia Recruiting NCT03933163 Phase 2 Resveratrol
41 A Double-Blind, Placebo-controlled Study on the Effects of MIN-102 on Biochemical, Imaging, Neurophisyiological, and Clinical Markers in Patients With Friedreich's Ataxia Active, not recruiting NCT03917225 Phase 2 MIN-102;Placebo
42 A Phase 2 Study of the Safety, Efficacy, and Pharmacodynamics of RTA 408 in the Treatment of Friedreich's Ataxia (MOXIe) Active, not recruiting NCT02255435 Phase 2 Omaveloxolone Capsules, 2.5 mg;Omaveloxolone Capsules, 5 mg;Omaveloxolone Capsules, 10 mg;Placebo;Omaveloxolone Capsules, 20 mg;Omaveloxolone Capsules, 40 mg;Omaveloxolone Capsules, 80 mg;Omaveloxolone Capsules, 160 mg;Omaveloxolone Capsules, 300 mg;Omaveloxolone Capsules, 150 mg
43 Effect of Nilotinib in Cerebellar Ataxia Patients Active, not recruiting NCT03932669 Phase 2 Nilotinib
44 Emergency Use Protocol for EPI-743 in Acutely Ill Patients With Inherited Mitochondrial Respiratory Chain Disease Within 90 Days of End-of-Life Care Active, not recruiting NCT01370447 Phase 2 EPI-743
45 Ferrochelating Treatment in Patients Affected by "Neurodegeneration With Brain Iron Accumulation" (NBIA) Active, not recruiting NCT00907283 Phase 2 Deferiprone
46 A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicentre Study of the Efficacy and Safety of Nicotinamide in Patients With Friedreich Ataxia Not yet recruiting NCT03761511 Phase 2 Nicotinamide;Placebo
47 A Phase 2 Clinical Trial to Test the Safety and Efficacy of Etravirine in Friedreich Ataxia Patients Not yet recruiting NCT04273165 Phase 2 Etravirine Tablets
48 Phase I Clinical Trial to Establish the Maximum Tolerated Dose of Idebenone in Children, Adolescents, and Adults With Friedreich's Ataxia Completed NCT00015808 Phase 1 Idebenone
49 Phase 1B Clinical Trial to Establish the Safety and Tolerability of a Multiple-Dose Regimen of Idebenone Administered to Patients With Friedreich's Ataxia Completed NCT00078481 Phase 1 Idebenone
50 A Phase 1, Randomized, Double-blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Oral VP 20629 in Adult Subjects With Friedreich's Ataxia Completed NCT01898884 Phase 1 VP 20629;Placebo

Search NIH Clinical Center for Friedreich Ataxia

Cochrane evidence based reviews: friedreich ataxia

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Genetic Tests for Friedreich Ataxia

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Genetic tests related to Friedreich Ataxia:

# Genetic test Affiliating Genes
1 Friedreich Ataxia 1 29 FXN
2 Friedreich's Ataxia 29
3 Friedreich Ataxia with Retained Reflexes 29
Sources

Anatomical Context for Friedreich Ataxia

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MalaCards organs/tissues related to Friedreich Ataxia:

40
Heart, Brain, Spinal Cord, Eye, Testes, Cerebellum, Liver
Sources

Publications for Friedreich Ataxia

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Articles related to Friedreich Ataxia:

(show top 50) (show all 1162)
# Title Authors PMID Year
1
G130V, a common FRDA point mutation, appears to have arisen from a common founder. 24 6 61 56
10543403 1999
2
Why do some Friedreich's ataxia patients retain tendon reflexes? A clinical, neurophysiological and molecular study. 24 54 6 56
10399865 1999
3
Intrafamilial phenotypic variability in Friedreich ataxia associated with a G130V mutation in the FRDA gene. 61 56 24 54
11843702 2002
4
Inhibitory effects of expanded GAA.TTC triplet repeats from intron I of the Friedreich ataxia gene on transcription and replication in vivo. 54 61 56 24
9603975 1998
5
Atypical Friedreich ataxia caused by compound heterozygosity for a novel missense mutation and the GAA triplet-repeat expansion. 61 56 6
9150176 1997
6
The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. 61 54 24 56
8751856 1996
7
FXN methylation predicts expression and clinical outcome in Friedreich ataxia. 61 24 56
22522441 2012
8
Progressive GAA expansions in dorsal root ganglia of Friedreich's ataxia patients. 24 56 54
17262846 2007
9
Clinical and genetic study of Friedreich ataxia in an Australian population. 56 24 61
10533031 1999
10
The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. 56 24 61
9443873 1998
11
The Friedreich ataxia GAA triplet repeat: premutation and normal alleles. 24 61 56
9259271 1997
12
Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA trinucleotide repeat. 24 61 56
9245990 1997
13
Visual system involvement in patients with Friedreich's ataxia. 24 56
18931386 2009
14
Mitochondrial ferritin limits oxidative damage regulating mitochondrial iron availability: hypothesis for a protective role in Friedreich ataxia. 61 56 54
18815198 2009
15
Friedreich's ataxia: clinical pilot trial with recombinant human erythropoietin. 24 56
17702040 2007
16
Idebenone delays the onset of cardiac functional alteration without correction of Fe-S enzymes deficit in a mouse model for Friedreich ataxia. 56 54 61
15028670 2004
17
Up-regulation of c-Jun N-terminal kinase pathway in Friedreich's ataxia cells. 61 56 54
12393810 2002
18
Friedreich ataxia: effects of genetic understanding on clinical evaluation and therapy. 54 61 56
12020255 2002
19
Very late onset Friedreich's presenting as spastic tetraparesis without ataxia or neuropathy. 56 24
11425956 2001
20
Genetic analysis of early onset cerebellar ataxia with retained tendon reflexes in four Tunisian families. 56 24
11298681 2001
21
Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. 56 54 61
10767347 2000
22
Recent advances in the molecular pathogenesis of Friedreich ataxia. 61 54 56
10767311 2000
23
Friedreich ataxia: an overview. 56 54 61
10633128 2000
24
Generalized chorea in two patients harboring the Friedreich's ataxia gene trinucleotide repeat expansion. 24 56
9539351 1998
25
Evolution of the Friedreich's ataxia trinucleotide repeat expansion: founder effect and premutations. 56 24
9207112 1997
26
Correlation between left ventricular hypertrophy and GAA trinucleotide repeat length in Friedreich's ataxia. 24 56
9142000 1997
27
Clinical and genetic abnormalities in patients with Friedreich's ataxia. 24 56
8815938 1996
28
Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. 24 6
8596916 1996
29
Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. 56 24
7272714 1981
30
A novel deletion-insertion mutation identified in exon 3 of FXN in two siblings with a severe Friedreich ataxia phenotype. 61 6
21830088 2011
31
Low predisposition to instability of the Friedreich ataxia gene in Cuban population. 56 61
20569261 2010
32
Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management. 61 56
19440741 2010
33
Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARgamma pathway as a therapeutic target in Friedreich's ataxia. 54 56
19376812 2009
34
DNA methylation in intron 1 of the frataxin gene is related to GAA repeat length and age of onset in Friedreich ataxia patients. 56 61
18697824 2008
35
Friedreich ataxia. 61 56
18852343 2008
36
The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues. 61 56
18045775 2008
37
Frataxin gene point mutations in Italian Friedreich ataxia patients. 61 6
17703324 2007
38
Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life. 56 61
17498922 2007
39
The 25-foot walk velocity accurately measures real world ambulation in Friedreich ataxia. 56 61
17325285 2007
40
The GAA triplet-repeat is unstable in the context of the human FXN locus and displays age-dependent expansions in cerebellum and DRG in a transgenic mouse model. 61 56
17024371 2007
41
GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology. 56 61
16919418 2006
42
Friedreich ataxia: the oxidative stress paradox. 61 56
15615771 2005
43
Upregulation of expression from the FRDA genomic locus for the therapy of Friedreich ataxia. 61 54 24
12516053 2003
44
A cellular model for Friedreich Ataxia reveals small-molecule glutathione peroxidase mimetics as novel treatment strategy. 61 56
12417527 2002
45
Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. 54 56
11939898 2002
46
Co-existence of frataxin and cardiac troponin T gene mutations in a child with Friedreich Ataxia and familial hypertrophic cardiomyopathy. 61 54 24
11857753 2002
47
Frataxin knockin mouse. 56 61
11852098 2002
48
Dissecting the epidemiology of a trinucleotide repeat disease - example of FRDA in Finland. 61 56
11810294 2002
49
Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. 61 56
11175786 2001
50
Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae. 61 56
11030757 2000
Sources

Variations for Friedreich Ataxia

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ClinVar genetic disease variations for Friedreich Ataxia:

6 (show all 12) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FXN NM_000144.5(FXN):c.317T>G (p.Leu106Ter)SNV Pathogenic 3979 rs104894105 9:71668109-71668109 9:69053193-69053193
2 FXN NM_000144.5(FXN):c.385-2A>GSNV Pathogenic 3980 rs140987490 9:71679852-71679852 9:69064936-69064936
3 FXN NM_000144.5(FXN):c.460A>T (p.Ile154Phe)SNV Pathogenic 3981 rs104894106 9:71679929-71679929 9:69065013-69065013
4 FXN NM_000144.5(FXN):c.389G>T (p.Gly130Val)SNV Pathogenic 3982 rs104894107 9:71679858-71679858 9:69064942-69064942
5 FXN NM_000144.5(FXN):c.3G>T (p.Met1Ile)SNV Pathogenic 3983 rs104894108 9:71650701-71650701 9:69035785-69035785
6 FXN NM_000144.5(FXN):c.438C>G (p.Asn146Lys)SNV Pathogenic 549677 rs146818694 9:71679907-71679907 9:69064991-69064991
7 FXN FXN, (GAA)n REPEAT EXPANSION, IVS1NT expansion Pathogenic 561195 9:71652203-71652220 9:69037287-69037304
8 FXN NM_000144.5(FXN):c.157del (p.Arg53fs)deletion Pathogenic 3985 rs141935559 9:71650852-71650852 9:69035936-69035936
9 FXN NM_000144.5(FXN):c.371_376delinsTACACCTTGAGGACA (p.Asp124_Ser126delinsValHisLeuGluAspThr)indel Pathogenic 35514 rs886037630 9:71668163-71668168 9:69053247-69053252
10 FXN NM_000144.5(FXN):c.517T>G (p.Trp173Gly)SNV Likely pathogenic 3984 rs56214919 9:71687562-71687562 9:69072646-69072646
11 FXN NG_008845.2:g.6743_6746delinsGAAGGA[66]GAAGindel Likely benign 804267
12 FXN NM_000144.5(FXN):c.54A>G (p.Pro18=)SNV Benign 129120 rs2481598 9:71650752-71650752 9:69035836-69035836

UniProtKB/Swiss-Prot genetic disease variations for Friedreich Ataxia:

73
# Symbol AA change Variation ID SNP ID
1 FXN p.Asp122Tyr VAR_002428 rs142157346
2 FXN p.Gly130Val VAR_002429 rs104894107
3 FXN p.Ile154Phe VAR_002430 rs104894106
4 FXN p.Trp155Arg VAR_002431 rs138471431
5 FXN p.Arg165Cys VAR_008139 rs138034837
6 FXN p.Leu182Phe VAR_008140 rs139616452
7 FXN p.Leu106Ser VAR_016065 rs104894105
8 FXN p.Leu198Arg VAR_016066 rs144104124

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Expression for Friedreich Ataxia

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Search GEO for disease gene expression data for Friedreich Ataxia.
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Pathways for Friedreich Ataxia

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Pathways related to Friedreich Ataxia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Spinocerebellar ataxia 36
11.46 CACNA1A ATXN8OS ATXN2
2
Iron metabolism in placenta 1
10.03 TFRC ACO1
3
Mitochondrial iron-sulfur cluster biogenesis 65
9.58 LYRM4 FXN
Sources

GO Terms for Friedreich Ataxia

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Cellular components related to Friedreich Ataxia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 perinuclear region of cytoplasm GO:0048471 9.65 TFRC PPARG HFE FMR1 ATXN2
2 mitochondrial matrix GO:0005759 9.62 MIPEP LYRM4 FXN FTMT
3 cell GO:0005623 9.5 TTPA TFRC HFE FXN FTMT CACNA1A
4 HFE-transferrin receptor complex GO:1990712 9.16 TFRC HFE
5 L-cysteine desulfurase complex GO:1990221 8.62 LYRM4 FXN

Biological processes related to Friedreich Ataxia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 iron-sulfur cluster assembly GO:0016226 9.43 LYRM4 FXN
2 iron ion transport GO:0006826 9.4 TFRC FTMT
3 response to iron ion GO:0010039 9.37 HFE FXN
4 small molecule metabolic process GO:0044281 9.32 LYRM4 FXN
5 positive regulation of aconitate hydratase activity GO:1904234 9.26 FXN FTMT
6 positive regulation of succinate dehydrogenase activity GO:1904231 9.16 FXN FTMT
7 cellular iron ion homeostasis GO:0006879 9.02 TFRC HFE FXN FTMT ACO1
8 positive regulation of lyase activity GO:0051349 8.96 FXN FTMT

Molecular functions related to Friedreich Ataxia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ferric iron binding GO:0008199 8.96 FXN FTMT
2 ferroxidase activity GO:0004322 8.62 FXN FTMT
Sources

Sources for Friedreich Ataxia

About this section
3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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