Autopsy and Case Reports
Autopsy and Case Reports
Autopsy Case Report

Cardiomyopathy as the first manifestation of Friedreich's ataxia

Rafael Tuzino Leite Neves Maffei; Giulio de los Santos Fortuna; Luca Campolino Rosso; Pedro Dragone Pires; Ivan Rondelli

Downloads: 3
Views: 1202


We present the case of a female patient diagnosed in childhood with Friedreich Ataxia (FA). At the age of 6, she developed left congestive heart failure with cardiomyopathy, as evident on echocardiogram. Neurologic signs only appeared at age 7, including marked loss of muscle mass, gait instability, muscle clonus, and Babinski's signal. At age 27, she had a stroke and was hospitalized; a few days later, she had a cardiorespiratory arrest with asystole, leading to death. The autopsy disclosed severe cardiomyopathy and significant myocardial replacement with fibrosis; therefore, the cause of death was assumed to be heart failure. Compared to the literature, our case has some unique features, such as cardiac disease as the presenting manifestation instead of gait instability, which is the major initial sign in most FA cases. Since our patient was submitted to an autopsy, it was an opportunity to retrieve important data to confirm the diagnosis and to evaluate the pathophysiology of this entity, such as myocardium fibrosis and cerebellar degeneration. In summary, our case demonstrates that cardiac disease can be the first manifestation of FA, with eventual diagnostic and prognostic implications. In addition, the autopsy provided findings of severe cardiomyopathy associated with FA.


Friedreich Ataxia, Cerebellar Ataxia, Cardiomyopathies, Autopsy


Friedreich N. Über degenerative Atrophie der spinalen Hinterstränge (On degenerative atrophy of the spinal dorsal columns).

Virchows Arch Pathol Anat Physiol Klin Med. 1863;26:391-419. [].

Foury F, Cazzalini O. Deletion of the yeast homologue of the human gene associated with Friedreich’s ataxia elicits iron accumulation in mitochondria.

FEBS Lett. 1997;411(2-3):373-7. []. [PMID:9271239]

Koutnikova H, Campuzano V, Foury F, Dollé P, Cazzalini O, Koenig M. Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin.

Nat Genet. 1997;16(4):345-51. []. [PMID:9241270]

Delatycki MB, Williamson R, Forrest SM. Friedreich ataxia: An overview.

J Med Genet. 2000;37(1):1-8. []. [PMID:10633128]

Emond M, Lepage G, Vanasse M, Pandolfo M. Increased levels of plasma malondialdehyde in Friedreich ataxia.

Neurology. 2000;55(11):1752-3. []. [PMID:11113241]

Schulz TJ, Thierbach R, Voigt A, et al. Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited.

J Biol Chem. 2006;281(2):977-81. []. [PMID:16263703]

Corben LA, Lynch D, Pandolfo M, Schulz JB, Delatycki MB. Consensus clinical management guidelines for Friedreich ataxia.

Orphanet J Rare Dis. 2014;9(1):184. []. [PMID:25928624]

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):1169-75. []. [PMID:8815938]

Payne RM, Wagner GR. Cardiomyopathy in Friedreich ataxia: clinical findings and research.

J Child Neurol. 2012;27(9):1179-86. []. [PMID:22764179]

Geoffroy G, Barbeau A, Breton G, et al. Clinical description and roentgenologic evaluation of patients with Friedreich’s ataxia.

Can J Neurol Sci. 1976;3(4):279-86. []. [PMID:1087179]

Filla A, De Michele G, Coppola G, et al. Accuracy of clinical diagnostic criteria for Friedreich’s ataxia.

Mov Disord. 2000;15(6):1255-8. [<1255::AID-MDS1031>3.0.CO;2-C]. [PMID:11104216]

de la Grandmaison GL, Clairand I, Durigon M. Organ weights in 684 adult autopsies: new tables for a Caucasoid population.

Forensic Sci Int. 2001;119(2):149-54. []. [PMID:11376980]

Bogliolo L, Brasileiro FG.

Bogliolo Patologia. ed Rio de Janeiro: Guanabara Koogan; 2006.

Delatycki MB, Corben LA. Clinical features of Friedreich ataxia.

J Child Neurol. 2012;27(9):1133-7. []. [PMID:22752493]

Pandolfo M. Friedreich ataxia: the clinical picture.

J Neurol. 2009;256(S1, Suppl 1):3-8. []. [PMID:19283344]

Santos R, Lefevre S, Sliwa D, Seguin A, Camadro JM, Lesuisse E. Friedreich ataxia: Molecular mechanisms, redox considerations, and therapeutic opportunities.

Antioxid Redox Signal. 2010;13(5):651-90. []. [PMID:20156111]

Reetz K, Dogan I, Costa AS, et al. Biological and clinical characteristics of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS) cohort: A cross‐sectional analysis of baseline data.

Lancet Neurol. 2015;14(2):174-82. []. [PMID:25566998]

Parkinson MH, Boesch S, Nachbauer W, Mariotti C, Giunti P. Clinical features of Friedreich’s ataxia: classical and atypical phenotypes.

J Neurochem. 2013;126(Suppl 1):103-17. []. [PMID:23859346]

Tsou AY, Paulsen EK, Lagedrost SJ, et al. Mortality in Friedreich ataxia.

J Neurol Sci. 2011;307(1-2):46-9. []. [PMID:21652007]

De Michele G, Perrone F, Filla A, et al. Age of onset, sex, and cardiomyopathy as predictors of disability and survival in Friedreich’s disease: A retrospective study on 119 patients.

Neurology. 1996;47(5):1260-4. []. [PMID:8909440]

Weidemann F, Rummey C, Bijnens B, et al. The heart in Friedreich ataxia: definition of cardiomyopathy, disease severity, and correlation with neurological symptoms.

Circulation. 2012;125(13):1626-34.

Koeppen AH. Friedreich’s ataxia: pathology, pathogenesis, and molecular genetics.

J Neurol Sci. 2011;303(1–2):1-12. []. [PMID:21315377]

Weidemann F, Störk S, Liu D, et al. Cardiomyopathy of Friedreich ataxia.

J Neurochem. 2013;126(Suppl 1):88-93. []. [PMID:23859344]

Gonzalez-Cabo P, Palau F. Mitochondrial pathophysiology in Friedreich’s ataxia.

J Neurochem. 2013;1(Suppl 1):53-64. []. [PMID:23859341]

Puccio H, Koenig M. Recent advances in the molecular pathogenesis of Friedreich ataxia.

Hum Mol Genet. 2000;9(6):887-92. []. [PMID:10767311]

Llorens JV, Soriano S, Calap-Quintana P, Gonzalez-Cabo P, Moltó MD. The role of iron in Friedreich’s ataxia: Insights from studies in human tissues and cellular and animal models.

Front Neurosci. 2019;13:75. []. [PMID:30833885]

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;9(2):275-82. []. [PMID:10607838]

Pandolfo M, Pastore A. The pathogenesis of Friedreich ataxia and the structure and function of frataxin.

J Neurol. 2009;256(S1, Suppl.):9-17. []. [PMID:19283345]

Babcock M, de Silva D, Oaks R, et al. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin.

Science. 1997;276(5319):1709-12. []. [PMID:9180083]

Koeppen AH, Mazurkiewicz JE. Friedreich ataxia: neuropathology revised.

J Neuropathol Exp Neurol. 2013;72(2):78-90. []. [PMID:23334592]

Schulz JB, Boesch S, Burk K, et al. Diagnosis and treatment of Friedreich ataxia: a European perspective.

Nat Rev Neurol. 2009;5(4):222-34. []. [PMID:19347027]






































Submitted date:

Accepted date:

Publication date:

5f5a21830e88258420cdcc41 autopsy Articles
Links & Downloads

Autops Case Rep

Share this page
Page Sections