Ataxia de Friedreich, revisión y actualización de la literatura con búsqueda sistemática de casos en Latinoamérica
Resumen
La Ataxia de Friedreich (AF) es una enfermedad neurodegenerativa autosómica recesiva con compromiso multisistémico. En esta revisión, se actualizan aspectos epidemiológicos, fisiopatológicos y clínico-terapéuticos y se conduce una búsqueda sistemática de casos de AF reportados en Latinoamérica. La prevalencia de AF en
poblaciones caucásicas es estimada entre 2 y 5 casos por 100 000 habitantes. En Latinoamérica se han publicado 35 estudios que reúnen 1481 casos en 6 países. Causada por la expansión anormal de repeticiones GAA en el gen FXN, la etiopatogenia está asociada a una reducción en los niveles de la proteína frataxina (que altera el metabolismo energético) y el acúmulo de hierro mitocondrial. El fenotipo clásico de AF suele comenzar antes de los 25 años, aunque hay otros de inicio tardío y retención de reflejos. La sintomatología se caracteriza por ataxia progresiva, alteración sensitiva, arreflexia, disartria, y alteraciones oculomotoras, además de compromiso cardiaco, endocrino y musculoesquelético. El diagnóstico requiere evaluación neurológica detallada, estudios neurofisiológicos, neuroimágenes y pruebas bioquímicas pero el enfoque determinante es el estudio genético que demuestre variantes genéticas bialélicas en el gen FXN. El manejo es multidisciplinario, orientado a aminorar los síntomas, prevenir complicaciones y brindar asesoramiento genético apropiado. Recientemente se ha aprobado el primer tratamiento farmacológico para AF con varios más en fases de experimentación.
Referencias
Harding AE. Friedreich’s ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features. Brain J Neurol.1981;104(3):589-620.
Campuzano V, Montermini L, Moltò MD, Pianese L, Cossée M, Cavalcanti F, et al. Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science.1996;271(5254):1423-7.
Friedreich N. Ueber degenerative Atrophie der spinalen Hinterstränge. Arch Für Pathol Anat Physiol Für Klin Med.1863;26(3):391-419.
Friedreich N. Ueber Ataxie mit besonderer Berücksichtigung der hereditären Formen. Arch Für Pathol Anat Physiol Für Klin Med.1877;70(1):140-52.
P M. Sur l’heredo-ataxie cerebelleuse. Sem Med.1893;13:444-7.
Chamberlain S, Shaw J, Rowland A, Wallis J, South S, Nakamura Y, et al. Mapping of mutation causing Friedreich’s ataxia to human chromosome 9. Nature. 1988;334(6179):248-50.
Vankan P. Prevalence gradients of Friedreich’s ataxia and R1b haplotype in Europe co-localize, suggesting a common Palaeolithic origin in the Franco-Cantabrian ice age refuge. J Neurochem.2013;126 Suppl 1:11-20.
Juvonen V, Kulmala SM, Ignatius J, Penttinen M, Savontaus ML. Dissecting the epidemiology of a trinucleotide repeat disease - example of FRDA in Finland. Hum Genet.2002;110(1):36-40.
Labuda M, Labuda D, Miranda C, Poirier J, Soong BW, Barucha NE, et al. Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion. Neurology.2000;54(12):2322-4.
Albano LMJ, Nishioka SAD, Moysés RL, Wagenführ J, Bertola D, Sugayama SMM, et al. Friedreich’s ataxia: cardiac evaluation of 25 patients with clinical diagnosis and literature review. Arq Bras Cardiol.2002;78(5):444-51.
Zeigelboim BS, Mesti JC, Fonseca VR, Faryniuk JH, Marques JM, Cardoso RC, et al. Otoneurological Abnormalities in Patients with Friedreich’s Ataxia. Int Arch Otorhinolaryngol.2017;21(1):79-85.
Rezende TJR, Martinez ARM, Faber I, Girotto Takazaki KA, Martins MP, de Lima FD, et al. Developmental and neurodegenerative damage in Friedreich’s ataxia. Eur J Neurol. 2019;26(3):483-9.
Boll MC, Gasca-Saldaña D, Mayén-Lobo YG, Dávila-Ortiz de Montellano DJ, Monroy-Jaramillo N. Clinical and Molecular Features of First Mexican Friedreich’s Ataxia Patients with Compound Heterozygous FXN Mutations. Neurol India. 2021;69(5):1363-7.
Cornejo-Olivas M, Inca-Martinez M, Castilhos RM, Furtado GV, Mattos EP, Bampi GB, et al. Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance.Cerebellum.2020;19(2):208-15.
Peluzzo TM, Bonadia LC, Donatti A, Molck MC, Jardim LB, Marques W, et al. Frequency and Genetic Profile of Compound Heterozygous Friedreich’s Ataxia Patients-the Brazilian Experience. Cerebellum.2019;18(6):1143-6.
Fussiger H, Saraiva-Pereira ML, Leistner-Segal S, Jardim LB. Friedreich Ataxia: Diagnostic Yield and Minimal Frequency in South Brazil.Cerebellum.2019;18(1):147-51.
Rezende TJR, Adanyeguh IM, Arrigoni F, Bender B, Cendes F, Corben LA, et al. Progressive Spinal Cord Degeneration in Friedreich’s Ataxia: Results from ENIGMA-Ataxia. Mov Disord. 2023;38(1):45-56.
Harding IH, Chopra S, Arrigoni F, Boesch S, Brunetti A, Cocozza S, et al. Brain Structure and Degeneration Staging in Friedreich Ataxia: Magnetic Resonance Imaging Volumetrics from the ENIGMA-Ataxia Working Group. Ann Neurol. 2021;90(4):570-83.
Takazaki KAG, Rezende TJR, Martinez ARM, Gonzalez-Salazar C, Nucci A, Lopes-Cendes I, et al. Sudomotor dysfunction is frequent and correlates with disability in Friedreich ataxia. Clin Neurophysiol Off J Int Fed Clin Neurophysiol. 2018;129(11):2290-5.
Takazaki KAG, Quinaglia T, Venancio TD, Martinez ARM, Shah RV, Neilan TG, et al. Pre-clinical left ventricular myocardial remodeling in patients with Friedreich’s ataxia: A cardiac MRI study. PloS One. 2021;16(3):e0246633.
Silva CB da, Yasuda CL, D’Abreu A, Cendes F, Lopes-Cendes I, França MC. Neuroanatomical correlates of depression in Friedreich’s ataxia: a voxel-based morphometry study. Cerebellum.2013;12(3):429-36.
Vieira Karuta SC, Raskin S, de Carvalho Neto A, Gasparetto EL, Doring T, Teive HAG. Diffusion tensor imaging and tract-based spatial statistics analysis in Friedreich’s ataxia patients. Parkinsonism Relat Disord.2015;21(5):504-8.
Rezende TJR, Martinez ARM, Faber I, Girotto K, Pedroso JL, Barsottini OG, et al. Structural signature of classical versus late-onset friedreich’s ataxia by Multimodality brain MRI. Hum Brain Mapp.2017;38(8):4157-68.
Rezende TJR, Silva CB, Yassuda CL, Campos BM, D’Abreu A, Cendes F, et al. Longitudinal magnetic resonance imaging study shows progressive pyramidal and callosal damage in Friedreich’s ataxia. Mov Disord Off J Mov Disord Soc.2016;31(1):70-8.
Zeigelboim BS, Teive HAG, Rosa MR da, Malisky JS, Fonseca VR, Marques JM, et al. The importance of central auditory evaluation in Friedreich’s ataxia. Arq Neuropsiquiatr.2018;76(3):170-6.
Bonilha da Silva C, Bergo FPG, D’Abreu A, Cendes F, Lopes-Cendes I, França MC. Dentate nuclei T2 relaxometry is a reliable neuroimaging marker in Friedreich’s ataxia. Eur J Neurol.2014;21(8):1131-6.
França MC, D’Abreu A, Yasuda CL, Bonadia LC, Santos da Silva M, Nucci A, et al. A combined voxel-based morphometry and 1H-MRS study in patients with Friedreich’s ataxia. J Neurol.2009;256(7):1114-20.
Musegante AFA, Almeida PNS, Monteiro RTM, Barroso Jr U. Urinary Symptoms and Urodynamics Findings in Patients with Friedreich’s Ataxia. Int Braz J Urol. 2013;39:867-74.
Albano LM, Zatz M, Kim CA, Bertola D, Sugayama SM, Marques-Dias MJ, et al. Friedreich’s ataxia: clinical and molecular study of 25 Brazilian cases. Rev Hosp Clin. 2001;56(5):143-8.
Salomão RPA, Gama MTD, Rezende Filho FM, Maggi F, Pedroso JL, Barsottini OGP. Late-Onset Friedreich’s Ataxia (LOFA) Mimicking Charcot-Marie-Tooth Disease Type 2: What Is Similar and What Is Different?. Cerebellum.2017;16(2):599-601.
Rangel DM, Nóbrega PR, Saraiva-Pereira ML, Jardim LB, Braga-Neto P. A case series of hereditary cerebellar ataxias in a highly consanguineous population from Northeast Brazil. Parkinsonism Relat Disord.2019;61:193-7.
Moro A, Martinez ARM, Karuta SCV, Munhoz RP, Moscovich M, Germiniani FMB, et al. «Pseudo-Dominant» Inheritance in Friedreich’s Ataxia: Clinical and Genetic Study of a Brazilian Family. Mov Disord Clin Pract.2014;1(4):361-3.
Pérez Akly M, Alvarez F. Ataxia de Friedreich de inicio tardío: Descripción clínica en una familia argentina. Med BAires. 2013;457-60.
Cardozo-Hernández AL de C, Rezende TJR, França MC. Hereditary spastic paraplegia type 11 (SPG11) is associated with obesity and hypothalamic damage. J Neurol Sci.2020;416:116982.
Schwartz IV, Jardim LB, Puga AC, Cocozza S, Leistner S, Lima LC. Clinical and molecular studies in five Brazilian cases of Friedreich ataxia. Arq Neuropsiquiatr.1999;57(1):1-5.
Martinez ARM, Moro A, Abrahao A, Faber I, Borges CR, Rezende TJR, et al. Nonneurological Involvement in Late-Onset Friedreich Ataxia (LOFA): Exploring the Phenotypes. Cerebellum.2017;16(1):253-6.
Pedraza O, Amaya M. Ataxias heredodegenerativas. Tesis de Grado. Bogota: Universidad del Rosario; 2013. https://repository.urosario.edu.co/bitstream/handle/10336/4606/PedrazaLinares-OlgaLucia-2013.pdf?sequence=1
Cervantes Arriaga A, Rodríguez Violante M, Villar Velarde A, Vargas Cañas S. Cardiomiopatía hipertrófica en ataxia de Friedreich. Presentación de dos casos. Gac Médica México. 2009;145(4):343-6.
Abrahao A, Pedroso JL, de Carvalho Aguiar PM, Barsottini OGP. Gene Expression Profile in Peripheral Blood Cells of Friedreich Ataxia Patients. Cerebellum Lond Engl.2016;15(3):306-13.
Santos TA, Maistro CEB, Silva CB, Oliveira MS, França MC, Castellano G. MRI Texture Analysis Reveals Bulbar Abnormalities in Friedreich Ataxia. AJNR Am J Neuroradiol.2015;36(12):2214-8.
Rasmussen A, Gómez M, Alonso E, Bidichandani SI. Clinical heterogeneity of recessive ataxia in the Mexican population. J Neurol Neurosurg Psychiatry.2006;77(12):1370-2.
Gómez M, Clark RM, Nath SK, Bhatti S, Sharma R, Alonso E, et al. Genetic admixture of European FRDA genes is the cause of Friedreich ataxia in the Mexican population. Genomics.2004;84(5):779-84.
Cruz-Mariño T, González-Zaldivar Y, Laffita-Mesa JM, Almaguer-Mederos L, Aguilera-Rodríguez R, Almaguer-Gotay D, et al. Uncommon features in Cuban families affected with Friedreich ataxia. Neurosci Lett.2010;472(2):85-9.
Chevis CF, da Silva CB, D’Abreu A, Lopes-Cendes I, Cendes F, Bergo FPG, et al. Spinal cord atrophy correlates with disability in Friedreich’s ataxia. Cerebellum Lond Engl. 2013;12(1):43-7.
Galea CA, Huq A, Lockhart PJ, Tai G, Corben LA, Yiu EM, et al. Compound heterozygous FXN mutations and clinical outcome in friedreich ataxia. Ann Neurol.2016;79(3):485-95.
Monrós E, Moltó MD, Martínez F, Cañizares J, Blanca J, Vílchez JJ, et al. Phenotype correlation and intergenerational dynamics of the Friedreich ataxia GAA trinucleotide repeat. Am J Hum Genet.1997;61(1):101-10.
Epplen C, Epplen JT, Frank G, Miterski B, Santos EJM, Schöls L. Differential stability of the (GAA)n tract in the Friedreich ataxia (STM7) gene. Hum Genet.1997;99(6):834-6.
Bürk K. Friedreich Ataxia: current status and future prospects. Cerebellum Ataxias.2017;4(1):4.
Greene E, Mahishi L, Entezam A, Kumari D, Usdin K. Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res. 2007;35(10):3383-90.
Cook A, Giunti P. Friedreich’s ataxia: clinical features, pathogenesis and management. Br Med Bull.2017;124(1):19-30.
Castro IH, Pignataro MF, Sewell KE, Espeche LD, Herrera MG, Noguera ME, et al. Frataxin Structure and Function. Subcell Biochem. 2019;93:393-438.
González-Cabo P, Palau F. Mitochondrial pathophysiology in Friedreich’s ataxia. J Neurochem. 2013;126(s1):53-64.
Bolinches-Amorós A, Mollá B, Pla-Martín D, Palau F, González-Cabo P. Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism. Front Cell Neurosci.2014;8:124.
Maio N, Rouault TA. Outlining the Complex Pathway of Mammalian Fe-S Cluster Biogenesis. Trends Biochem Sci.2020;45(5):411-26.
Cai K, Frederick RO, Tonelli M, Markley JL. Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine desulfurase complex leading to Fe-S cluster assembly. J Inorg Biochem.2018;183:107-16.
Haugen AC, Di Prospero NA, Parker JS, Fannin RD, Chou J, Meyer JN, et al. Altered Gene Expression and DNA Damage in Peripheral Blood Cells from Friedreich’s Ataxia Patients: Cellular Model of Pathology. PLoS Genet.2010;6(1):e1000812.
Clark E, Johnson J, Dong YN, Mercado-Ayon E, Warren N, Zhai M, et al. Role of frataxin protein deficiency and metabolic dysfunction in Friedreich ataxia, an autosomal recessive mitochondrial disease. Neuronal Signal.2018;2(4):NS20180060.
Khan W, Corben LA, Bilal H, Vivash L, Delatycki MB, Egan GF, et al. Neuroinflammation in the Cerebellum and Brainstem in Friedreich Ataxia: An [18F]-FEMPA PET Study. Mov Disord.2022;37(1):218-24.
Kemp KC, Cerminara N, Hares K, Redondo J, Cook AJ, Haynes HR, et al. Cytokine therapy-mediated neuroprotection in a Friedreich’s ataxia mouse model. Ann Neurol. 2017;81(2):212-26.
Apolloni S, Milani M, D’Ambrosi N. Neuroinflammation in Friedreich’s Ataxia. Int J Mol Sci. 2022;23(11):6297.
Koeppen AH, Mazurkiewicz JE. Friedreich Ataxia: Neuropathology Revised. J Neuropathol Exp Neurol. 2013;72(2):78-90.
Indelicato E, Nachbauer W, Eigentler A, Amprosi M, Gothe RM, Giunti P, et al. Onset features and time to diagnosis in Friedreich’s Ataxia. Orphanet J Rare Dis [Internet]. 2020 [citado 18 de enero de 2023];15(1). Disponible en: https://hal.sorbonne-universite.fr/hal-03268732
Poole ML, Wee JS, Folker JE, Corben LA, Delatycki MB, Vogel AP. Nasality in Friedreich ataxia. Clin Linguist Phon. 2015;29(1):46-58.
Morral JA, Davis AN, Qian J, Gelman BB, Koeppen AH. Pathology and pathogenesis of sensory neuropathy in Friedreich’s ataxia. Acta Neuropathol (Berl). 2010;120(1):97-108.
Bidichandani SI, Delatycki MB. Friedreich Ataxia [Internet]. GeneReviews® [Internet]. University of Washington, Seattle; 2017 [citado 31 de enero de 2023]. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK1281/
Reetz K, Dogan I, Hohenfeld C, Didszun C, Giunti P, Mariotti C, et al. Nonataxia symptoms in Friedreich Ataxia: Report from the Registry of the European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS). Neurology.2018;91(10):e917-30.
Seyer LA, Galetta K, Wilson J, Sakai R, Perlman S, Mathews K, et al. Analysis of the visual system in Friedreich ataxia. J Neurol.2013;260(9):2362-9.
Rojas P, de Hoz R, Cadena M, Salobrar-García E, Fernández-Albarral JA, López-Cuenca I, et al. Neuro-Ophthalmological Findings in Friedreich’s Ataxia. J Pers Med.2021;11(8):708.
Spieker S, Schulz JB, Petersen D, Fetter M, Klockgether T, Dichgans J. Fixation instability and oculomotor abnormalities in Friedreich’s ataxia. J Neurol. 1995;242(8):517-21.
Hocking DR, Fielding J, Corben LA, Cremer PD, Millist L, White OB, et al. Ocular motor fixation deficits in Friedreich ataxia. Cerebellum Lond Engl.2010;9(3):411-8.
Fahey MC, Cremer PD, Aw ST, Millist L, Todd MJ, White OB, et al. Vestibular, saccadic and fixation abnormalities in genetically confirmed Friedreich ataxia. Brain J Neurol.2008;131(Pt 4):1035-45.
Spoendlin H. Optic cochleovestibular degenerations in hereditary ataxias. II. Temporal bone pathology in two cases of Friedreich’s ataxia with vestibulo-cochlear disorders. Brain J Neurol.1974;97(1):41-8.
Paulus-Andres JA, Burnett MS. Three Adult-Onset Autosomal Recessive Ataxias: What Adult Neurologists Need to Know. Neurol Clin Pract.2021;11(3):256-62.
Tsou AY, Paulsen EK, Lagedrost SJ, Perlman SL, Mathews KD, Wilmot GR, et al. Mortality in Friedreich ataxia. J Neurol Sci.2011;307(1-2):46-9.
Payne RM, Wagner GR. Cardiomyopathy in Friedreich Ataxia: Clinical Findings and Research. J Child Neurol.2012;27(9):1179-86.
Hanson E, Sheldon M, Pacheco B, Alkubeysi M, Raizada V. Heart disease in Friedreich’s ataxia. World J Cardiol.2019;11(1):1-12.
Pousset F, Legrand L, Monin ML, Ewenczyk C, Charles P, Komajda M, et al. A 22-Year Follow-up Study of Long-term Cardiac Outcome and Predictors of Survival in Friedreich Ataxia. JAMA Neurol.2015;72(11):1334-41.
Kipps A, Alexander M, Colan SD, Gauvreau K, Smoot L, Crawford L, et al. The Longitudinal Course of Cardiomyopathy in Friedreich’s Ataxia During Childhood. Pediatr Cardiol.2009;30(3):306-10.
Tamaroff J, DeDio A, Wade K, Wells M, Park C, Leavens K, et al. Friedreich’s Ataxia related Diabetes: Epidemiology and management practices. Diabetes Res Clin Pract [Internet].2022 [citado 31 de enero de 2023];186. Disponible en: https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(22)00640-4/fulltext
Cnop M, Mulder H, Igoillo-Esteve M. Diabetes in Friedreich Ataxia. J Neurochem. 2013;126(s1):94-102.
Rummey C, Farmer JM, Lynch DR. Predictors of loss of ambulation in Friedreich’s ataxia. EClinicalMedicine.2020;18:100213.
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.
Galimanis A, Glutz L, Burgunder JM, Spiegel R, Kaelin-Lang A. Very-late-onset Friedreich ataxia with disturbing head tremor and without spinal atrophy--a case report. Mov Disord Off J Mov Disord Soc.2008;23(7):1058-9.
Coppola G, De Michele G, Cavalcanti F, Pianese L, Perretti A, Santoro L, et al. Why do some Friedreich’s ataxia patients retain tendon reflexes? A clinical, neurophysiological and molecular study. J Neurol.1999;246(5):353-7.
Verma R, Gupta M. Freidreich’s ataxia with retained reflexes: a phenotype and genotype correlation. BMJ Case Rep.2012;2012:bcr2012007496.
Corben LA, Lynch D, Pandolfo M, Schulz JB, Delatycki MB. Consensus clinical management guidelines for Friedreich ataxia. Orphanet J Rare Dis. 2014;9:184.
Richter A, Poirier J, Mercier J, Julien D, Morgan K, Roy M, et al. Friedreich ataxia in Acadian families from eastern Canada: clinical diversity with conserved haplotypes. Am J Med Genet.1996;64(4):594-601.
Alix JJP, Alam T, Garrard K, Martindale J, Shanmugarajah P, Ganesh Rao D, et al. Variable sensory nerve conduction parameters in late onset Friedreich ataxia. Muscle Nerve. 2017;55(2):E7-8.
Dogan I, Romanzetti S, Didszun C, Mirzazade S, Timmann D, Saft C, et al. Structural characteristics of the central nervous system in Friedreich ataxia: an in vivo spinal cord and brain MRI study. J Neurol Neurosurg Psychiatry.2019;90(5):615-7.
Monda E, Lioncino M, Rubino M, Passantino S, Verrillo F, Caiazza M, et al. Diagnosis and Management of Cardiovascular Involvement in Friedreich Ataxia. Heart Fail Clin.2022;18(1):31-7.
Muthuswamy S, Agarwal S, Dalal A. Diagnosis and Genetic Counseling for Friedreich’s Ataxia: A time for consideration of TP-PCR in an Indian Setup. Hippokratia. 2013;17(1):38-41.
Barsottini OGP, Albuquerque MVC de, Braga-Neto P, Pedroso JL. Adult onset sporadic ataxias: a diagnostic challenge. Arq Neuropsiquiatr. 2014;72(3):232-40.
Friedreich’s Ataxia Research Alliance - Clinical Care Guidelines [Internet]. [citado 31 de enero de 2023]. Disponible en: https://www.curefa.org/clinical-care-guidelines
Lynch DR, Chin MP, Delatycki MB, Subramony SH, Corti M, Hoyle JC, et al. Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study). Ann Neurol. 2021;89(2):212-25.
Lynch DR, Chin MP, Boesch S, Delatycki MB, Giunti P, Goldsberry A, et al. Efficacy of Omaveloxolone in Friedreich’s Ataxia: Delayed-Start Analysis of the MOXIe Extension. Mov Disord Off J Mov Disord Soc. 2023;38(2):313-20.
Research C for DE and. FDA approves first treatment for Friedreich’s ataxia. FDA [Internet]. 2023 [citado 23 de marzo de 2023]; Disponible en: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-friedreichs-ataxia
Zesiewicz TA, Hancock J, Ghanekar SD, Kuo SH, Dohse CA, Vega J. Emerging therapies in Friedreich’s Ataxia. Expert Rev Neurother. 2020;20(12):1215-28.
Ocana-Santero G, Díaz-Nido J, Herranz-Martín S. Future Prospects of Gene Therapy for Friedreich’s Ataxia. Int J Mol Sci. 2021;22(4):1815.
Sivakumar A, Cherqui S. Advantages and Limitations of Gene Therapy and Gene Editing for Friedreich’s Ataxia. Front Genome Ed. 2022;4:903139.
Byard RW, Gilbert JD. Mechanisms of unexpected death and autopsy findings in Friedreich ataxia. Med Sci Law. 2017;57(4):192-6.
Derechos de autor 2023 María Alfaro-Olivera, Adriana Calle-Nuñez, Alfonso Uribe-León, Wilfor Aguirre-Quispe, Elison Sarapura-Castro, Mario Cornejo-Olivas
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