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Hypertrophic cardiomyopathy in Friedreich's ataxia
International Journal of Cardiology 127 (2008) e122 – e123 www.elsevier.com/locate/ijcard
Letter to the Editor
Hypertrophic cardiomyopathy in Friedreich's ataxia A. Fayssoil a,⁎, O. Nardi b , D. Orlikowski b , D. Annane b a b
Service de Cardiologie 3, Hôpital Européen Georges Pompidou, Paris, France Service de Reanimation medicale, Hôpital Raymond Poincare, Garches, France Received 31 January 2007; accepted 12 April 2007 Available online 30 July 2007
Abstract Friedreich's ataxia is an autosomal recessive disorder characterized by spinocerebellar degeneration. It is caused by a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9 (9q13). We reported a case of hypertrophic cardiomyopathy associated with Friedreich's ataxia in a twenty year old patient. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Friedreich's ataxia; Frataxin; Hypertrophic cardiomyopathy; Echocardiography
A twenty year old patient was admitted in our unit for cardiopulmonary explorations because of Friedreich's ataxia. His past medical history was pertinent for Friedreich's disease known since 1989, vertebral arthrodesis in 2005. The diagnosis was confirmed by genetic analysis. She was disabled (wheelchair). Electrocardiogram showed sinusal rythm with electrical biventricular hypertrophy. Echocardiography disclosed hypertrophic concentric cardiomyopathy with 15 mm of septal thickness and 17 mm of left ventricular posterior wall thickness without intraventricular obstruction. Left ventricular contraction was normal (Ejection fraction = 57%). Friedreich's ataxia is an autosomal recessive disorder. It is caused by a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9 (9q13) [1]. It is characterized by spinocerebellar degeneration which is associated often to heart disease and diabetes mellitus. Heart manifestation is represented by left ventricular hypertrophy [2]. Analysis of the GAA triplet is a strong molecular tool for clinical diagnosis, genetic counselling and prenatal diagnosis [3]. The physiopathology underlying is not well known. There is a good correlation between size of the expanded repeat and severity of the phenotype [4]. Frataxin is a mitochondrial protein which plays a role in iron homeostasis [3,4]. Deficiency of frataxin results in mitochondrial iron accumulation, defects in specific mitochondrial enzymes. The ⁎ Corresponding author. E-mail address: [email protected] (A. Fayssoil). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.04.109
oxidative phosphorylation in frataxin deficiency is disturbed by the ironinduced oxygen radical [3]. Idebenone is a promising treatment [5]. Buyse G et al. [5], in a study including eight patients, found after one year of therapy by Ibederone, a significant reduction of cardiac hypertrophy in six of eight patients. The reduction of hypertrophy was preceded by an early improvement in cardiac function on strain and strain rate imaging in echocardiography. This case emphasized the need for echocardiography in Friedreich's ataxia because of hypertrophic cardiomyopathy often associated.
A. Fayssoil et al. / International Journal of Cardiology 127 (2008) e122–e123
Hypertrophic Cardiomyopathy: left ventricular posterior wall (17 mm) with pericardial effusion (12 mm). References [1] Bit-Avragim N, Perrot A, Schols L, et al. The GAA repeat expansion in intron 1 of the frataxin gene is related to the severity of cardiac manifestation in patients with Friedreich's ataxia. J Mol Med 2001;78 (11):626–32.
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[2] Van der Hauwaert LG, Dumoulin M. Hypertrophic cardiomyopathy in Friedreich's ataxia. Br Heart J Dec 1976;38(12):1291–8. [3] Palau F. Friedreich's ataxia and frataxin: molecular genetics, evolution and pathogenesis (Review). Int J Mol Med Jun 2001;7(6):581–9. [4] Alper G, Narayanan V. Friedreich's ataxia. Pediatr Neurol May 2003;28 (5):335–41. [5] Buyse G, Mertens L, Di Salvo G, et al. Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring. Neurology May 27 2003;60(10):1679–81.
Letter to the Editor
Hypertrophic cardiomyopathy in Friedreich's ataxia A. Fayssoil a,⁎, O. Nardi b , D. Orlikowski b , D. Annane b a b
Service de Cardiologie 3, Hôpital Européen Georges Pompidou, Paris, France Service de Reanimation medicale, Hôpital Raymond Poincare, Garches, France Received 31 January 2007; accepted 12 April 2007 Available online 30 July 2007
Abstract Friedreich's ataxia is an autosomal recessive disorder characterized by spinocerebellar degeneration. It is caused by a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9 (9q13). We reported a case of hypertrophic cardiomyopathy associated with Friedreich's ataxia in a twenty year old patient. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Friedreich's ataxia; Frataxin; Hypertrophic cardiomyopathy; Echocardiography
A twenty year old patient was admitted in our unit for cardiopulmonary explorations because of Friedreich's ataxia. His past medical history was pertinent for Friedreich's disease known since 1989, vertebral arthrodesis in 2005. The diagnosis was confirmed by genetic analysis. She was disabled (wheelchair). Electrocardiogram showed sinusal rythm with electrical biventricular hypertrophy. Echocardiography disclosed hypertrophic concentric cardiomyopathy with 15 mm of septal thickness and 17 mm of left ventricular posterior wall thickness without intraventricular obstruction. Left ventricular contraction was normal (Ejection fraction = 57%). Friedreich's ataxia is an autosomal recessive disorder. It is caused by a mutation that consists of an unstable expansion of GAA repeats in the first intron of the gene encoding frataxin on chromosome 9 (9q13) [1]. It is characterized by spinocerebellar degeneration which is associated often to heart disease and diabetes mellitus. Heart manifestation is represented by left ventricular hypertrophy [2]. Analysis of the GAA triplet is a strong molecular tool for clinical diagnosis, genetic counselling and prenatal diagnosis [3]. The physiopathology underlying is not well known. There is a good correlation between size of the expanded repeat and severity of the phenotype [4]. Frataxin is a mitochondrial protein which plays a role in iron homeostasis [3,4]. Deficiency of frataxin results in mitochondrial iron accumulation, defects in specific mitochondrial enzymes. The ⁎ Corresponding author. E-mail address: [email protected] (A. Fayssoil). 0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2007.04.109
oxidative phosphorylation in frataxin deficiency is disturbed by the ironinduced oxygen radical [3]. Idebenone is a promising treatment [5]. Buyse G et al. [5], in a study including eight patients, found after one year of therapy by Ibederone, a significant reduction of cardiac hypertrophy in six of eight patients. The reduction of hypertrophy was preceded by an early improvement in cardiac function on strain and strain rate imaging in echocardiography. This case emphasized the need for echocardiography in Friedreich's ataxia because of hypertrophic cardiomyopathy often associated.
A. Fayssoil et al. / International Journal of Cardiology 127 (2008) e122–e123
Hypertrophic Cardiomyopathy: left ventricular posterior wall (17 mm) with pericardial effusion (12 mm). References [1] Bit-Avragim N, Perrot A, Schols L, et al. The GAA repeat expansion in intron 1 of the frataxin gene is related to the severity of cardiac manifestation in patients with Friedreich's ataxia. J Mol Med 2001;78 (11):626–32.
e123
[2] Van der Hauwaert LG, Dumoulin M. Hypertrophic cardiomyopathy in Friedreich's ataxia. Br Heart J Dec 1976;38(12):1291–8. [3] Palau F. Friedreich's ataxia and frataxin: molecular genetics, evolution and pathogenesis (Review). Int J Mol Med Jun 2001;7(6):581–9. [4] Alper G, Narayanan V. Friedreich's ataxia. Pediatr Neurol May 2003;28 (5):335–41. [5] Buyse G, Mertens L, Di Salvo G, et al. Idebenone treatment in Friedreich's ataxia: neurological, cardiac, and biochemical monitoring. Neurology May 27 2003;60(10):1679–81.