Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.
Friedreich ataxia (FA) is a rare, inherited, neurodegenerative condition affecting the brain, spinal cord, and peripheral nerves. Demyelination and atrophy of these nerves cause progressive deterioration of muscular coordination and strength, sensory impairments, and decline in independent mobility.1
Mutations in the FXN gene are the primary underlying cause of FA. These mutations result in the repeat expansion of the GAA (guanine-adenine-adenine) trinucleotide, which in turn causes decreased biosynthesis of the mitochondrial protein, frataxin. Frataxin is involved in iron metabolism and regulation, so deficiency of the protein leads to iron accumulation and deposition within the mitochondria and cells such as cardiomyocytes. Increased accumulation, deposition, and circulation of free iron leads to oxidative stress and tissue damage.2
The primary FA-related complication leading to mortality is the development of cardiac dysfunction, especially hypertrophic cardiomyopathy resulting in congestive heart failure or arrhythmias. Approximately two-thirds of patients with FA die from congestive heart failure or arrhythmias.3
Cardiac complications in FA are consequences of mitochondrial proliferation and the loss of contractile proteins leading to myocardial fibrosis. Additionally, increased iron deposition and iron-mediated oxidative tissue damage within the cardiomyocytes may contribute to the pathogenesis of cardiomyopathy.3
Hypertrophic cardiomyopathy, dilated cardiomyopathy, congestive heart failure, myocardial fibrosis, myocarditis, cardiomegaly, symmetrical hypertrophy of the heart, asymmetric septal hypertrophy, and arrhythmias including tachycardia and atrial fibrillation are possible complications resulting from this tissue damage and the loss of contractile fibers in the myocardium.2,3
Read more about FA pathophysiology
Another common metabolic, disease-related complication of FA is diabetes mellitus.1,3-5 The reported incidence of diabetes within this patient population ranges from 8% to 32%. Patients with FA and comorbid diabetes often experience an earlier onset of FA and have a longer FA disease duration.5
Patients with FA demonstrate increased susceptibility to developing diabetes than age-matched individuals from the general population. Often, diabetes onset is acute, requiring insulin at the time of diagnosis. If it occurs, hyperglycemia usually develops 15 years after the onset of neurological symptoms of FA.5
Some studies indicate a correlation between GAA trinucleotide expansion size and the development of insulin resistance.5-7 Other researchers did not find an association between GAA trinucleotide expansion size and diabetes.8-10
It is suspected that frataxin deficiency resulting in mitochondrial dysfunction may contribute to the development of diabetes in patients with FA, particularly when these mitochondrial defects affect metabolic processes within insulin target tissues and pancreatic beta cells.5
Read more about FA risk factors
Kyphoscoliosis gradually occurs due to neuromuscular imbalances around the spine in patients with FA. This may result in significant cardiopulmonary dysfunction and morbidity, as severe spinal curvatures may lead to restrictions in respiratory function.3
Foot deformities such as pes cavus and talipes equinovarus are common musculoskeletal clinical features of FA.11,12 Pes cavus, characterized by high plantar arches that do not flatten during gait, occurs in 55% to 75% of patients with FA. Pes cavus rarely causes morbidity. In contrast, equinovarus foot deformities are more likely to cause morbidity for patients with FA, disrupting balance and causing ambulation difficulties.11
Surgical intervention may be required to correct these musculoskeletal deformities if they become severe enough to interfere with independent mobility or organ function.3
Read more about FA surgical management
Urinary Incontinence/Overactive Bladder
Urinary incontinence or overactive bladder symptoms occur commonly in patients with FA. These symptoms include problems with urinary storage, urgency, frequency, and leakage. Urodynamic testing may reveal altered bladder capacity and uncontrolled detrusor contractions, contributing to these problems. Additionally, problems with voiding may also present, including urinary hesitancy, poor urine stream, feelings of incomplete bladder emptying, double voiding, and urinary retention, which may increase the risk of urinary tract infections in this patient population.13
One study of 140 patients with FA reported the prevalence of these symptoms to be around 23%.7 Overactive bladder is often treated with antimuscarinic medications.13
Read more about FA treatment
Friedreich ataxia also affects the muscular coordination necessary for efficient swallowing and speech. Diet modifications and swallowing strategies may assist patients with FA in maintaining independence with feeding and improve quality of life measures.14 Placement of a nasogastric or gastrostomy feeding tube may be necessary if dysphagia becomes severe and life-threatening secondary to aspiration or choking concerns.15
Dysarthria combined with hearing deficits makes communication, socialization, and education more difficult for patients, especially children, with FA.16
Read more about FA diet and nutrition
Vision and Hearing Loss
Reduced vision and hearing impairment are less frequent disease-related complications than cardiac, musculoskeletal, and endocrine complications.11 A loss of optic tract nerve fibers results in gradual vision loss.3
Researchers found that while children with FA were able to detect sounds in relatively normal ranges, severe deficits in auditory temporal processing and speech understanding exacerbated issues of dysarthria in these patients. Any hindrances in the perception of speech, especially during the years of speech/language development, can make the formation of accurate sounds when speaking more difficult.16
Read more about FA therapies
- Friedreich ataxia fact sheet. National Institute of Neurological Disorders and Stroke (NINDS). Accessed January 23, 2023.
- Hanson E, Sheldon M, Pacheco B, Alkubeysi M, Raizada V. Heart disease in Friedreich’s ataxia. World J Cardiol. 2019;11(1):1-12. doi:10.4330/wjc.v11.i1.1
- Williams CT, De Jesus O. Friedreich ataxia. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. Updated September 5, 2022. Accessed January 23, 2023.
- Ran S, Abeti R, Giunti P. Diabetes in Friedreich ataxia. In: Barbetti F, Ghizzoni L, Guaraldi F, eds. Diabetes Associated With Single Gene Defects and Chromosomal Abnormalities. Vol 25. Basel, Switzerland: Karger Publishers; 2017:172-181.
- Cnop M, Mulder H, Igoillo-Esteve M. Diabetes in Friedreich ataxia. J Neurochem. 2013;126(s1):94-102. doi:10.1111/jnc.12216
- Hebinck J, Hardt C, Schöls L, et al. Heterozygous expansion of the GAA tract of the X25/frataxin gene is associated with insulin resistance in humans. Diabetes. 2000;49(9):1604-1607. doi:10.2337/diabetes.49.9.1604
- Filla A, De Michele G, Cavalcanti F, et al. The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am J Hum Genet. 1996;59(3):554-560.
- Dürr A, Cossee M, Agid Y, et al. Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N Engl J Med. 1996;335(16):1169-1175. doi:10.1056/NEJM199610173351601
- Mateo I, Llorca J, Volpini V, Corral J, Berciano J, Combarros O. Expanded GAA repeats and clinical variation in Friedreich’s ataxia. Acta Neurol Scand. 2004;109(1):75-78. doi:10.1034/j.1600-0404.2003.00190.x
- Montermini L, Richter A, Morgan K, et al. Phenotypic variability in Friedreich ataxia: role of the associated GAA triplet repeat expansion. Ann Neurol. 1997;41(5):675-682. doi:10.1002/ana.410410518
- Delatycki MB, Corben LA. Clinical features of Friedreich ataxia. J Child Neurol. 2012;27(9):1133-1137. doi:10.1177/0883073812448230
- Cook A, Giunti P. Friedreich’s ataxia: clinical features, pathogenesis and management. Br Med Bull. 2017;124(1):19-30. doi:10.1093/bmb/ldx034
- Management of the ataxias towards best clinical practice: third edition. Ataxia UK. July 2016. Accessed January 23, 2023.
- Vogel AP, Brown SE, Folker JE, Corben LA, Delatycki MB. Dysphagia and swallowing-related quality of life in Friedreich ataxia. J Neurol. 2014;261(2):392-399. doi:10.1007/s00415-013-7208-4
- Vogel AP, Keage MJ, Johansson K, Schalling E. Treatment for dysphagia (swallowing difficulties) in hereditary ataxia. Cochrane Database Syst Rev. 2015;11:CD010169. doi:10.1002/14651858.CD010169.pub2
- Rance G, Corben L, Delatycki M. Auditory processing deficits in children with Friedreich ataxia. J Child Neurol. 2012;27(9):1197-1203. doi:10.1177/0883073812448963
Reviewed by Kyle Habet, MD, on 1/23/2023.