Cardiac Transplantation in Friedreich Ataxia

Yoon, Grace; Soman, Teesta; Wilson, Judith; George, Kristen M; Mital, Seema; Dipchand, Anne I.; McCabe, Jane; Logan, William J.; Kantor, Paul F.

doi:10.1177/0883073812448229

Cited by 10 publications

(7 citation statements)

References 21 publications

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“…The major cardiovascular signs/symptoms described in FRDA are CMP (57–81%) [ 16 ]. The age of onset ranges from the end of 1st decade to the end of 2nd decade of life.…”

Section: Resultsmentioning

confidence: 99%

Myocardial and Arrhythmic Spectrum of Neuromuscular Disorders in Children

Baban¹,

Lodato²,

Parlapiano

et al. 2021

Biomolecules

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Neuromuscular disorders (NMDs) are highly heterogenous from both an etiological and clinical point of view. Their signs and symptoms are often multisystemic, with frequent cardiac involvement. In fact, childhood onset forms can predispose a person to various progressive cardiac abnormalities including cardiomyopathies (CMPs), valvulopathies, atrioventricular conduction defects (AVCD), supraventricular tachycardia (SVT) and ventricular arrhythmias (VA). In this review, we selected and described five specific NMDs: Friedreich’s Ataxia (FRDA), congenital and childhood forms of Myotonic Dystrophy type 1 (DM1), Kearns Sayre Syndrome (KSS), Ryanodine receptor type 1-related myopathies (RYR1-RM) and Laminopathies. These changes are widely investigated in adults but less researched in children. We focused on these specific topics due their relative frequency and their potential unexpected cardiac manifestations in children. Moreover these conditions present different inheritance patterns and mechanisms of action. We decided not to discuss Duchenne and Becker muscular dystrophies due to extensive work regarding the cardiac aspects in children. For each described NMD, we focused on the possible cardiac manifestations such as different types of CMPs (dilated-DCM, hypertrophic-HCM, restrictive-RCM or left ventricular non compaction-LVNC), structural heart abnormalities (including valvulopathies), and progressive heart rhythm changes (AVCD, SVT, VA). We describe the current management strategies for these conditions. We underline the importance, especially for children, of a serial multidisciplinary personalized approach and the need for periodic surveillance by a dedicated heart team. This is largely due to the fact that in children, the diagnosis of certain NMDs might be overlooked and the cardiac aspect can provide signs of their presence even prior to overt neurological diagnosis.

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“…The major cardiovascular signs/symptoms described in FRDA are CMP (57–81%) [ 16 ]. The age of onset ranges from the end of 1st decade to the end of 2nd decade of life.…”

Section: Resultsmentioning

confidence: 99%

Myocardial and Arrhythmic Spectrum of Neuromuscular Disorders in Children

Baban¹,

Lodato²,

Parlapiano

et al. 2021

Biomolecules

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“…The anti-oxidant idebenone reportedly benefits FRDA cardiomyopathy, but well-controlled studies did not yield a positive effect on the neurologic phenotype (51, 61). A few case reports of cardiac transplantation in FRDA have appeared (62). Although causative therapy of FRDA is not yet available, patients clearly benefit from drug treatment of their heart disease and diabetes mellitus, physical therapy, and surgical control of progressive scoliosis.…”

Section: Pathogenesis Of Frdamentioning

confidence: 99%

Friedreich Ataxia: Neuropathology Revised

Koeppen

Mazurkiewicz

2013

J Neuropathol Exp Neurol

217

233

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Friedreich ataxia is an autosomal recessive disorder that affects children and young adults. The mutation consists of a homozygous guanine-adenine-adenine trinucleotide repeat expansion that causes deficiency of frataxin, a small nuclear genome–encoded mitochondrial protein. Low frataxin levels lead to insufficient biosynthesis of iron-sulfur clusters that are required for mitochondrial electron transport and assembly of functional aconitase, and iron dysmetabolism of the entire cell. This review of the neuropathology of Friedreich ataxia stresses the critical role of hypoplasia and superimposed atrophy of dorsal root ganglia. Progressive destruction of dorsal root ganglia accounts for thinning of dorsal roots, degeneration of dorsal columns, transsynaptic atrophy of nerve cells in Clarke column and dorsal spinocerebellar fibers, atrophy of gracile and cuneate nuclei, and neuropathy of sensory nerves. The lesion of the dentate nucleus consists of progressive and selective atrophy of large glutamatergic neurons and grumose degeneration of corticonuclear synaptic terminals that contain γ-aminobutyric acid (GABA). Small GABA-ergic neurons and their projection fibers in the dentato-olivary tract survive. Atrophy of Betz cells and corticospinal tracts constitute a second intrinsic CNS lesion. In light of the selective vulnerability of organs and tissues to systemic frataxin deficiency, many questions about the pathogenesis of Friedreich ataxia remain.

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“…The three patients in this series add to the literature of four previously reported heart transplants in patients with heart failure and FRDA [11][12][13][14]. Here, though, the individuals have been followed since their transplant for extended periods of time.…”

Section: Discussionmentioning

confidence: 86%

“…Ethical considerations must be taken into account for patients who are potential candidates for heart transplantation but present with progressive neurologic disease. Multidisciplinary forums must address an array of complex issues, including utility, quality of life, justice, life expectancy, and contraindications when considering heart transplant allocation within in the setting of FRDA [11,14,17]. We previously reported that the mean age of death in FRDA is 36.5 years, with 59% of deaths caused by cardiac dysfunction [18].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there is no known cure for FRDA cardiomyopathy and much controversy surrounds the design and implementation of appropriate therapeutic intervention, with little standardization in this population [11]. Four previous case reports demonstrate the short-term success of cardiac transplantation in abating life-threatening cardiomyopathy [11][12][13][14]. In this paper, we describe three additional patients with mild-to-moderate neurologic disease but severe cardiac dysfunction who subsequently underwent successful cardiac transplantation.…”

Section: Introductionmentioning

confidence: 92%

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Cardiac transplantation in Friedreich Ataxia: Extended follow-up

McCormick

Shinnick

Schadt

et al. 2017

Journal of the Neurological Sciences

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Friedreich Ataxia (FRDA) is an autosomal recessive neurodegenerative disorder most commonly caused by guanine-adenine-adenine (GAA) trinucleotide repeat expansions in both alleles of the FXN gene. Although progressive ataxia remains the hallmark clinical feature, patients with FRDA are at high risk of developing cardiomyopathy, often resulting in premature death. There is no specific treatment for FRDA-associated cardiomyopathy; even in advanced cardiac failure cardiac transplantation is not commonly pursued. This case series describes extended follow-up of three FRDA cases with end-stage heart failure but mild neurologic disease who underwent successful heart transplantation. We also review and examine the ethical considerations for heart transplantation in the setting of neurodegenerative disease.

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Cardiac Transplantation in Friedreich Ataxia

Cited by 10 publications

References 21 publications

Myocardial and Arrhythmic Spectrum of Neuromuscular Disorders in Children

Myocardial and Arrhythmic Spectrum of Neuromuscular Disorders in Children

Friedreich Ataxia: Neuropathology Revised

Cardiac transplantation in Friedreich Ataxia: Extended follow-up

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