Medical Care

As previously discussed, GAA repeat expansion along with the reduced effect on frataxin expression is the main known cause of Friedreich ataxia (FA). No approved therapy to delay, stop, or reverse the progression of FA is available in the United States. Free radical scavengers, specific inhibitors of histone deacetylases, and antioxidants (eg, coenzyme Q, N-acetylcysteine, vitamin E) are being studied.^[14]

Antioxidant therapy with idebenone, in particular, has been extensively studied for the treatment of FA.^{[15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30]}Idebenone potentially improves mitochondrial function and decreases production of reactive oxygen species. However, it has not been shown to increase exercise capacity or significantly alter neurologic function.^{[31, 32]}

Supportive treatment should be provided as needed. Diabetes must be managed. Cardiac failure and arrhythmias should be treated as they arise.

Surgical Care

Surgery for foot deformity and scoliosis may be of benefit in selected patients. Current guidelines should provide assistance in making this determination (see Guidelines).^[3]

Prevention

Prenatal testing is clinically available for couples at a 25% risk of having a child with FA and in whom both disease-causing mutations are known.^[33]DNA extracted from cells obtained from amniocentesis at 16-18 weeks of gestation or chorionic villus sampling at 9-11 weeks of gestation can be analyzed.

Consultations

Consultations that may be helpful include the following:

Genetic counselor for DNA testing
Orthopedic surgeon for scoliosis and cavovarus foot deformities ^{[34, 35]}
Cardiologist for evaluation of cardiomyopathy
Endocrinologist for diabetes mellitus management
Rehabilitation medicine therapist for prostheses, walking aids, wheelchairs, and physical, occupational, and speech therapy

Guidelines

Pandolfo M. Friedreich ataxia. Arch Neurol. 2008 Oct. 65 (10):1296-303. [QxMD MEDLINE Link].
Bürk K. Friedreich Ataxia: current status and future prospects. Cerebellum Ataxias. 2017. 4:4. [QxMD MEDLINE Link].
[Guideline] Corben LA, Collins V, Milne S, Farmer J, Musheno A, Lynch D, et al. Clinical management guidelines for Friedreich ataxia: best practice in rare diseases. Orphanet J Rare Dis. 2022 Nov 12. 17 (1):415. [QxMD MEDLINE Link]. [Full Text].
Bidichandani SI, Delatycki MB. Friedreich Ataxia. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al, eds. GeneReviews. Seattle, WA: University of Washington; 2017 Jun 1. [Full Text].
Bradley JL, Blake JC, Chamberlain S, Thomas PK, Cooper JM, Schapira AH. Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. Hum Mol Genet. 2000 Jan 22. 9 (2):275-82. [QxMD MEDLINE Link].
Wells RD. DNA triplexes and Friedreich ataxia. FASEB J. 2008 Jun. 22 (6):1625-34. [QxMD MEDLINE Link].
Evidente VG, Gwinn-Hardy KA, Caviness JN, Gilman S. Hereditary ataxias. Mayo Clin Proc. 2000 May. 75 (5):475-90. [QxMD MEDLINE Link].
Kostrzewa M, Klockgether T, Damian MS, Müller U. Locus heterogeneity in Friedreich ataxia. Neurogenetics. 1997 May. 1 (1):43-7. [QxMD MEDLINE Link].
Martin JB. Molecular basis of the neurodegenerative disorders. N Engl J Med. 1999 Jun 24. 340 (25):1970-80. [QxMD MEDLINE Link].
Friedreich ataxia. MedlinePlus. Available at https://ghr.nlm.nih.gov/condition/friedreich-ataxia#genes. July 2, 2021; Accessed: November 22, 2022.
Becker AB, Qian J, Gelman BB, Yang M, Bauer P, Koeppen AH. Heart and Nervous System Pathology in Compound Heterozygous Friedreich Ataxia. J Neuropathol Exp Neurol. 2017 Aug 1. 76 (8):665-675. [QxMD MEDLINE Link].
Puccio H, Koenig M. Recent advances in the molecular pathogenesis of Friedreich ataxia. Hum Mol Genet. 2000 Apr 12. 9 (6):887-92. [QxMD MEDLINE Link].
Wood NW. Diagnosing Friedreich's ataxia. Arch Dis Child. 1998 Mar. 78 (3):204-7. [QxMD MEDLINE Link]. [Full Text].
Petrillo S, D'Amico J, La Rosa P, Bertini ES, Piemonte F. Targeting NRF2 for the Treatment of Friedreich's Ataxia: A Comparison among Drugs. Int J Mol Sci. 2019 Oct 21. 20 (20):[QxMD MEDLINE Link]. [Full Text].
Pandolfo M. Drug Insight: antioxidant therapy in inherited ataxias. Nat Clin Pract Neurol. 2008 Feb. 4 (2):86-96. [QxMD MEDLINE Link].
Tonon C, Lodi R. Idebenone in Friedreich's ataxia. Expert Opin Pharmacother. 2008 Sep. 9 (13):2327-37. [QxMD MEDLINE Link].
Tsou AY, Friedman LS, Wilson RB, Lynch DR. Pharmacotherapy for Friedreich ataxia. CNS Drugs. 2009. 23 (3):213-23. [QxMD MEDLINE Link].
Meier T, Perlman SL, Rummey C, Coppard NJ, Lynch DR. Assessment of neurological efficacy of idebenone in pediatric patients with Friedreich's ataxia: data from a 6-month controlled study followed by a 12-month open-label extension study. J Neurol. 2012 Feb. 259 (2):284-91. [QxMD MEDLINE Link].
Idebenone to treat Friedreich's ataxia. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT00229632. March 18, 2019; Accessed: November 22, 2022.
Schulz JB, Di Prospero NA, Fischbeck K. Clinical experience with high-dose idebenone in Friedreich ataxia. J Neurol. 2009 Mar. 256 Suppl 1 (0 1):42-5. [QxMD MEDLINE Link].
Meier T, Buyse G. Idebenone: an emerging therapy for Friedreich ataxia. J Neurol. 2009 Mar. 256 Suppl 1:25-30. [QxMD MEDLINE Link].
Tonon C, Lodi R. Idebenone in Friedreich's ataxia. Expert Opin Pharmacother. 2008 Sep. 9 (13):2327-37. [QxMD MEDLINE Link].
Pineda M, Arpa J, Montero R, Aracil A, Domínguez F, Galván M, et al. Idebenone treatment in paediatric and adult patients with Friedreich ataxia: long-term follow-up. Eur J Paediatr Neurol. 2008 Nov. 12 (6):470-5. [QxMD MEDLINE Link].
Di Prospero NA, Sumner CJ, Penzak SR, Ravina B, Fischbeck KH, Taylor JP. Safety, tolerability, and pharmacokinetics of high-dose idebenone in patients with Friedreich ataxia. Arch Neurol. 2007 Jun. 64 (6):803-8. [QxMD MEDLINE Link].
Di Prospero NA, Baker A, Jeffries N, Fischbeck KH. Neurological effects of high-dose idebenone in patients with Friedreich's ataxia: a randomised, placebo-controlled trial. Lancet Neurol. 2007 Oct. 6 (10):878-86. [QxMD MEDLINE Link].
Rai M, Soragni E, Jenssen K, Burnett R, Herman D, Coppola G, et al. HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PLoS One. 2008 Apr 9. 3 (4):e1958. [QxMD MEDLINE Link]. [Full Text].
Willis JH, Isaya G, Gakh O, Capaldi RA, Marusich MF. Lateral-flow immunoassay for the frataxin protein in Friedreich's ataxia patients and carriers. Mol Genet Metab. 2008 Aug. 94 (4):491-497. [QxMD MEDLINE Link]. [Full Text].
Soragni E, Herman D, Dent SY, Gottesfeld JM, Wells RD, Napierala M. Long intronic GAA*TTC repeats induce epigenetic changes and reporter gene silencing in a molecular model of Friedreich ataxia. Nucleic Acids Res. 2008 Nov. 36 (19):6056-65. [QxMD MEDLINE Link]. [Full Text].
Correia AR, Pastore C, Adinolfi S, Pastore A, Gomes CM. Dynamics, stability and iron-binding activity of frataxin clinical mutants. FEBS J. 2008 Jul. 275 (14):3680-90. [QxMD MEDLINE Link].
Strawser C, Schadt K, Hauser L, McCormick A, Wells M, Larkindale J, et al. Pharmacological therapeutics in Friedreich ataxia: the present state. Expert Rev Neurother. 2017 Sep. 17 (9):895-907. [QxMD MEDLINE Link].
Drinkard BE, Keyser RE, Paul SM, Arena R, Plehn JF, Yanovski JA, et al. Exercise capacity and idebenone intervention in children and adolescents with Friedreich ataxia. Arch Phys Med Rehabil. 2010 Jul. 91 (7):1044-50. [QxMD MEDLINE Link]. [Full Text].
Lynch DR, Perlman SL, Meier T. A phase 3, double-blind, placebo-controlled trial of idebenone in friedreich ataxia. Arch Neurol. 2010 Aug. 67 (8):941-7. [QxMD MEDLINE Link].
Pandolfo M, Montermini L. Prenatal diagnosis of Friedreich ataxia. Prenat Diagn. 1998 Aug. 18 (8):831-3. [QxMD MEDLINE Link].
Shapiro F, Specht L. The diagnosis and orthopaedic treatment of childhood spinal muscular atrophy, peripheral neuropathy, Friedreich ataxia, and arthrogryposis. J Bone Joint Surg Am. 1993 Nov. 75 (11):1699-714. [QxMD MEDLINE Link].
Milbrandt TA, Kunes JR, Karol LA. Friedreich's ataxia and scoliosis: the experience at two institutions. J Pediatr Orthop. 2008 Mar. 28 (2):234-8. [QxMD MEDLINE Link].

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Author

Stephen Kishner, MD, MHA Clinical Professor, Louisiana State University School of Medicine in New Orleans

Stephen Kishner, MD, MHA is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Paul E Di Cesare, MD Clinical Operations Associate Medical Director, AIM Specialty Health

Paul E Di Cesare, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Vinod K Panchbhavi, MD, FACS, FAOA, FABOS, FAAOS Professor, Department of Orthopedic Surgery, Chief, Division of Foot and Ankle Surgery, Director, Foot and Ankle Fellowship Program, Department of Orthopedic Surgery, University of Texas Medical Branch School of Medicine

Vinod K Panchbhavi, MD, FACS, FAOA, FABOS, FAAOS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, American Orthopaedic Foot and Ankle Society, Orthopaedic Trauma Association, Texas Orthopaedic Association

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Styker.

Additional Contributors

Jegan Krishnan, MBBS, FRACS, PhD Professor, Chair, Department of Orthopedic Surgery, Flinders University of South Australia; Senior Clinical Director of Orthopedic Surgery, Repatriation General Hospital; Private Practice, Orthopaedics SA, Flinders Private Hospital

Jegan Krishnan, MBBS, FRACS, PhD is a member of the following medical societies: Australian Medical Association, Australian Orthopaedic Association, Royal Australasian College of Surgeons

Disclosure: Nothing to disclose.

Acknowledgements

Natalya V Bulaeva, MD, PhD, and John Baker, MD, are gratefully acknowledged for their contributions to this article.

Sections Orthopedic Surgery for Friedreich Ataxia
Overview
Presentation
DDx
Workup
Treatment
Guidelines
References

Orthopedic Surgery for Friedreich Ataxia Treatment & Management

Medical Care

Surgical Care

Prevention

Consultations

References

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