Friedreich ataxia (FRDA) 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 puberty¹.

Prevalence

1 50,000

1/50,000^1,2: Known carrier frequency 1000/100,000; observed 421/100,000. Most common inherited ataxia in Europe, the Middle East, India, and North Africa; not documented in Southeast Asia, in sub-Saharan Africa, or among Native Americans³.

Age of Onset

Typical: 10-15; Range: 2-80³.

HPO Terms

HP:0000505 Visual impairment HP:0000639 Nystagmus HP:0000648 Optic atrophy HP:0000649 Abnormality of visual evoked potentials HP:0000763 Sensory neuropathy HP:0000819 Diabetes mellitus HP:0001123 Visual field defect HP:0001251 Ataxia HP:0001260 Dysarthria HP:0001626 Abnormality of the cardiovascular system HP:0001635 Congestive heart failure HP:0001639 Hypertrophic cardiomyopathy HP:0001761 Pes cavus HP:0002066 Gait ataxia HP:0002070 Limb ataxia HP:0002495 Impaired vibratory sensation HP:0002522 Areflexia of lower limbs HP:0002650 Scoliosis HP:0003115 Abnormal EKG HP:0003209 Decreased pyruvate carboxylase activity HP:0003232 Mitochondrial malic enzyme reduced HP:0003448 Decreased sensory nerve conduction velocity HP:0003487 Babinski sign HP:0007078 Decreased amplitude of sensory action potentials HP:0007663 Reduced visual acuity HP:0010831 Impaired proprioception

Association

Mendelian

Locus

hg19 chr9:71652202-71652220

hg38 chr9:69037286-69037304

t2t chr9:81210834-81210861

Details

96% of FA patients have biallelic GAA expansions in intron 1 (compared to compound heterozygous with another mutation type), in which the reference allele is conventionally 5-33 repeats³. Intermediate alleles (34-55) are associated with premutations, but may lead to disease as exact pathogenicity/penetrance thresholds have not been demarcated. Dysphagia is highly prevalent and progressive^4,3. The expanded repeats can be interrupted with GAAGAG, GAAGGA, or GAAGAAAA sequences, leading to differential phenotypes⁵. Allele size is correlated with disease severity and inversely correlated to age of onset⁶. ~20% of patients carry an expanded composite (GAA-GGA) allele with large tracts of tandem GGA triplets near the 5' end of the repeat (median ~44, range 22-342), with further minor interruptions occurring in ~10% of cases⁷.

Mechanism

LoF

Loss of function via transcriptional silencing^8,9.

Detection

RP-PCR and long-range PCR have been used to detect expansions¹⁰. Standard long-range PCR and RP-PCR poorly amplify GC rich expanded composite (GAA-GGA) alleles and fail to detect proximal FXN deletions, so affected individuals may be misclassified as homozygous for expansions, though composite alleles are recovered through the addition of 7-deaza-dGTP⁷. Long-read sequencing has sized large alleles and resolved sequence organization, including proximal deletions^10,7.

Year

1996¹¹

Location in Gene

Intron 1

Gene Strand

Alleles

Ref. Motif

GAA

Ranges

Benign (ref.)

–

Benign (gene)

–

Pathogenic (ref.)

AAG

Pathogen. (gene)

AAG

Unknown (ref.)

–

Unknown (gene)

–

Interruption (ref.)

–

Interrup. (gene)

–

gnomAD

References

Direct supporting references for info on this page.

1omim:229300

Profiling of Short-Tandem-Repeat Disease Alleles in 12,632 Human Whole Genomes.

Haibao,Tang, Ewen F,Kirkness, Christoph,Lippert, William H,Biggs, Martin,Fabani, Ernesto,Guzman, Smriti,Ramakrishnan, Victor,Lavrenko, Boyko,Kakaradov, Claire,Hou, Barry,Hicks, David,Heckerman, Franz J,Och, C Thomas,Caskey, J Craig,Venter, Amalio,Telenti

American journal of human genetics · 2017-11-02

pmid:29100084

Friedreich Ataxia

Sanjay I.,Bidichandani, Martin B.,Delatycki, Marek,Napierala, Antoine,Duquette

GeneReviews® · 1993-01-01

genereviews:NBK1281

Dysphagia in Friedreich Ataxia.

Megan J,Keage, Martin B,Delatycki, Isabelle,Gupta, Louise A,Corben, Adam P,Vogel

Dysphagia · 2017-05-04

pmid:28474131

Sequence variation in GAA repeat expansions may cause differential phenotype display in Friedreich's ataxia.

D O,McDaniel, B,Keats, V V,Vedanarayanan, S H,Subramony

Movement disorders : official journal of the Movement Disorder Society · 2001-11-01

pmid:11748752

Clinical and genetic abnormalities in patients with Friedreich's ataxia.

A,Dürr, M,Cossee, Y,Agid, V,Campuzano, C,Mignard, C,Penet, J L,Mandel, A,Brice, M,Koenig

The New England journal of medicine · 1996-10-17

pmid:8815938

Unrecognized high prevalence of expanded composite repeats in Friedreich ataxia.

Morgan C,Devore, Christina,Lam, Graham,Wiley, Courtney C,Park, David R,Lynch, Sanjay I,Bidichandani

Human molecular genetics · 2026-02-10

pmid:41432640

Diseases of unstable repeat expansion: mechanisms and common principles.

Jennifer R,Gatchel, Huda Y,Zoghbi

Nature reviews. Genetics · 2005-10-01

pmid:16205714

Clinical and neuroimaging review of triplet repeat diseases.

Ryo,Kurokawa, Mariko,Kurokawa, Akihiko,Mitsutake, Moto,Nakaya, Akira,Baba, Yasuhiro,Nakata, Toshio,Moritani, Osamu,Abe

Japanese journal of radiology · 2022-09-28

pmid:36169768

A Comprehensive Triple-Repeat Primed PCR and a Long-Range PCR Agarose-Based Assay for Improved Genotyping of Guanine-Adenine-Adenine Repeats in Friedreich Ataxia.

Mohamed,Jama, Rebecca L,Margraf, Ping,Yu, N Scott,Reading, Pinar,Bayrak-Toydemir

The Journal of molecular diagnostics : JMD · 2022-05-17

pmid:35595154

Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion.

V,Campuzano, L,Montermini, M D,Moltò, L,Pianese, M,Cossée, F,Cavalcanti, E,Monros, F,Rodius, F,Duclos, A,Monticelli, F,Zara, J,Cañizares, H,Koutnikova, S I,Bidichandani, C,Gellera, A,Brice, P,Trouillas, G,De Michele, A,Filla, R,De Frutos, F,Palau, P I,Patel, S,Di Donato, J L,Mandel, S,Cocozza, M,Koenig, M,Pandolfo

Science (New York, N.Y.) · 1996-03-08

pmid:8596916

Additional Literature

Additional literature related to this locus.

Raw PubMed search results
(All PubMed results returned by searching for this gene, tandem repeats, and disease, in medline format)

Limiting intestinal iron absorption rescues glial defects and extends lifespan in a Drosophila model of Friedreich's ataxia.

Ema,Turki, Estelle,Jullian, Pierre,Delamotte, Anne,Filipe, Laura,Tixier-Cardoso, Sandrine,Middendorp, Elodie,Martin, Véronique,Monnier

Neurobiology of disease · 2026-07-29

pmid:42526774

Dysregulation of sphingolipid-metabolizing enzymes in Friedreich's ataxia:

Zenouska,Ramchunder, Ester,Kalef-Ezra, Saqlain,Suleman, Fred Jonathan,Edzeamey, Sandor,Szunyogh, Owen,Gittins, Natalia,Castro Mena, Richard,Wade-Martins, Adamo,Valle, Charareh,Pourzand, Sara,Anjomani Virmouni

iScience · 2026-06-22

pmid:42383006

Frataxin deficiency drives cardiac dysfunction and transcriptional dysregulation in Friedreich ataxia iPSC model.

Jarmon G,Lees, Haoxiang,Zhang, Lebei,Jiao, Anne M,Kong, Ren Jie,Phang, Li,Li, Nan,Su, Sebastian,Bass-Stringer, Hei-Yi H,Woo, Anthony S,Mukhtar, Alice,Pébay, Mirella,Dottori, Louise,Corben, Martin,Delatycki, Roger,Peverill, Stephen,Wilcox, Jarny,Choi, Jeffrey M,Pullin, Davis,McCarthy, Jill S,Napierala, Marek,Napierala, Shiang Y,Lim

Cell death & disease · 2026-06-23

pmid:42331777

Assessing airway clearance dysfunction in Friedreich's ataxia: A focus on peak cough flow.

Barbara K,Smith, Mackenzi A,Coker, Cristina,Liberati, Blake P,Meyer, Samantha,Norman, Jessica,Ehrbar, Carmen,Leon-Astudillo, Sub,Subramony, Manuela,Corti

Journal of neuromuscular diseases · 2026-06-08

pmid:42253100

Compound Heterozygote Friedreich Ataxia Patients With Covert Proximal FXN Gene Deletions.

Michael P,Lazaropoulos, Morgan C,Devore, Christina,Lam, Courtney,Park, Sanjay,Bidichandani, David R,Lynch

Annals of clinical and translational neurology · 2026-06-02

pmid:42227166

Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich's ataxia models.

Jeffrey,Pido-Lopez, Shefta E,Moula, Enas,Shaban, Konstantinos,Stamatiou, Bethan J,Critchley, Thomas E,Whittaker, Stina,Svensson, Sara,Anjomani-Virmouni, Ester,Kalef-Ezra, Lucinda,Carr, Jane,Hassel, Adrian J,Thrasher, Manju A,Kurian, Ian A,Blair, Teerapat,Rojsajjakul, Giorgia,Santilli, Arturo,Sala

Cell reports. Medicine · 2026-05-13

pmid:42134333

Genome-wide detection and clinical prioritization of tandem repeat outliers using long-read sequencing.

Sophia B,Gibson, Nikhita,Damaraju, J Gus,Gustafson, Elsa V,Balton, Sirisak,Chanprasert, Ian A,Glass, Martha,Horike-Pyne, Runjun D,Kumar, Kathleen A,Leppig, Chris,Lundberg, Jane,Ranchalis, Elisabeth A,Rosenthal, Andrew K,Solomon, Andrew B,Stergachis, Mark,Wener, Gail P,Jarvik, Elizabeth E,Blue, Katrina M,Dipple, Harriet,Dashnow, Lea M,Starita, Danny E,Miller

medRxiv : the preprint server for health sciences · 2026-05-01

pmid:42094143

The TRKB Agonist 7,8-dihydroxyflavone Alleviates DNA Damage and Apoptosis in a Neuronal Cell Model of Friedreich's Ataxia.

Jorge,Galán-Cruz, Andrés,Vicente-Acosta, Frida,Loría, Javier,Díaz-Nido, Saúl,Herranz-Martín

Molecular neurobiology · 2026-04-22

pmid:42018061

Longitudinal analysis shows GAA1 length and baseline clinical status as robust predictors of progression in Friedreich ataxia.

Leire,Manrique, Francisco,Martínez-Dubarbie, Ana L,Pelayo-Negro, Natalia,Benitez-Calle, María Victoria,Sanchez-Pelaez, Daniel,Cota-Gonzalez, Ruben,Loza, Raquel,Martinez-Díaz, Juan,Irure-Ventura, Coro,Sanchez-Quintana, Ivelisse,Sanchez, Antoni,Matilla-Dueñas, Jon,Infante

Journal of neurology · 2026-04-09

pmid:41954755

Locus FRDA FXN

Disease

Locus

Alleles

gnomAD

References

Additional Literature