Download PDF
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2017; 75(06): 339-344
DOI: 10.1590/0004-282X20170044
ARTICLE

Autosomal recessive spastic ataxia of Charlevoix-Saguenay: a family report from South Brazil

Ataxia espástica autossçmica recessiva de Charlevoix-Saguenay: relato de uma família do sul do Brasil
Daniela Burguêz
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
2   Hospital de Clínicas de Porto Alegre, Laboratório de Identificação Genética, Porto Alegre RS, Brasil;
,
Camila Maria de Oliveira
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
,
Marcio Aloísio Bezerra Cavalcanti Rockenbach
3   Hospital de Clínicas de Porto Alegre, Serviço de Radiologia, Porto Alegre RS, Brasil;
,
Helena Fussiger
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
,
Leonardo Modesti Vedolin
3   Hospital de Clínicas de Porto Alegre, Serviço de Radiologia, Porto Alegre RS, Brasil;
4   Universidade Federal do Rio Grande do Sul, Departamento de Medicina Interna, Porto Alegre RS, Brasil.
,
Pablo Brea Winckler
5   Hospital de Clínicas de Porto Alegre, Serviço de Neurologia, Porto Alegre RS, Brasil;
,
Marcelo Krieger Maestri
6   Hospital de Clínicas de Porto Alegre, Serviço de Oftalmologia, Porto Alegre RS, Brasil;
,
Alessandro Finkelsztejn
5   Hospital de Clínicas de Porto Alegre, Serviço de Neurologia, Porto Alegre RS, Brasil;
,
Filippo Maria Santorelli
7   Molecular Medicine-Neurogenetics, IRCCS-Fondazione Stella Maris, Pisa, Italy;
,
Laura Bannach Jardim
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
2   Hospital de Clínicas de Porto Alegre, Laboratório de Identificação Genética, Porto Alegre RS, Brasil;
8   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Medicina: Ciências Médicas, Porto Alegre RS, Brasil.
4   Universidade Federal do Rio Grande do Sul, Departamento de Medicina Interna, Porto Alegre RS, Brasil.
,
Jonas Alex Morales Saute
1   Hospital de Clínicas de Porto Alegre, Serviço de Genética Médica, Porto Alegre RS, Brasil;
2   Hospital de Clínicas de Porto Alegre, Laboratório de Identificação Genética, Porto Alegre RS, Brasil;
8   Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Medicina: Ciências Médicas, Porto Alegre RS, Brasil.
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

ABSTRACT

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset, neurodegenerative disorder caused by mutations in SACS, firstly reported in Quebec, Canada. The disorder is typically characterized by childhood onset ataxia, spasticity, neuropathy and retinal hypermyelination. The clinical picture of patients born outside Quebec, however, is often atypical. In the present article, the authors describe clinical and neuroradiological findings that raised the suspicion of an ARSACS diagnosis in two female cousins with Germanic background from Rio Grande do Sul, Brazil. We present a review on the neuroimaging, ophthalmologic and neurophysiologic clues for ARSACS diagnosis. The early-onset, slowly progressive, spastic-ataxia phenotype of reported patients was similar to ARSACS patients from Quebec. The SACS sequencing revealed the novel homozygous c.5150_5151insA frameshift mutation confirming the ARSACS diagnosis. ARSACS is a frequent cause of early onset ataxia/spastic-ataxia worldwide, with unknown frequency in Brazil.

RESUMO

A ataxia espástica autossçmica recessiva de Charlevoix-Saguenay (ARSACS) é uma doença neurodegenerativa de início precoce causada por mutações no gene SACS que foi inicialmente descrita na região de Quebec, Canadá. A apresentação típica de ARSACS é caracterizada por ataxia, espasticidade, polineuropatia e hipermielinização das fibras nervosas da retina de início infantil. No presente artigo, descrevemos os achados clínicos e neurorradiológicos que levaram à suspeita de ARSACS em duas primas descendentes de alemães naturais do Rio Grande do Sul, Brasil e revisamos os achados de neuroimagem, oftalmológicos e neurofisiológicos de ARSACS. O fenótipo de ataxia-espástica de início infantil precoce apresentado pelas pacientes era similar ao classicamente descrito em Quebec. O sequenciamento do SACS revelou a mutação nova c.5150_5151insA (mudança na matriz de leitura), em homozigose, confirmando o diagnóstico de ARSACS. A ARSACS é uma causa frequente de ataxia/ataxia-espástica de início precoce mundialmente, entretanto sua frequência é desconhecida no Brasil.

cerebellar ataxia - spastic paraparesis - genetics - magnetic resonance imaging - ophthalmology
ataxia cerebelar - paraparesia espástica - genética - imagem por ressonância magnética - oftalmologia


Publication History

Received: 08 November 2016

Accepted: 14 February 2017

Article published online:
05 September 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Barbeau A, Bouchard R, Bouchard RW. Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Can J Neurol Sci. 1978;5(1):61-9.
  • 2 Bouchard JP, Richter A, Mathieu J, Brunet D, Hudson TJ, Morgan K et al. Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Neuromuscul Disord. 1998;8(7):474-9. https://doi.org/10.1016/S0960-8966(98)00055-8
  • 3 Richter A, Rioux JD, Bouchard JP, Mercier J, Mathieu J, Ge B et al. Location score and haplotype analyses of the locus for autosomal recessive spastic ataxia of Charlevoix-Saguenay, in chromosome region 13q11. Am J Hum Genet. 1999;64(3):768-75. https://doi.org/10.1086/302274
  • 4 Engert JC, Doré C, Mercier J, Ge B, Bétard C, Rioux JD et al. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): high-resolution physical and transcript map of the candidate region in chromosome region 13q11. Genomics. 1999;62(2):156-64. https://doi.org/10.1006/geno.1999.6003
  • 5 Engert JC, Bérubé P, Mercier J, Doré C, Lepage P, Ge B et al. ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet. 2000;24(2):120-5. https://doi.org/10.1038/72769
  • 6 Parfitt DA, Michael GJ, Vermeulen EG, Prodromou NV, Webb TR, Gallo JM et al. The ataxia protein sacsin is a functional co-chaperone that protects against polyglutamine-expanded ataxin-1. Hum Mol Genet. 2009;18(9):1556-65. https://doi.org/10.1093/hmg/ddp067
  • 7 Bouhlal Y, Amouri R, El Euch-Fayeche G, Hentati F. Autosomal recessive spastic ataxia of Charlevoix-Saguenay: an overview. Parkinsonism Relat Disord. 2011;17(6):418-22. https://doi.org/10.1016/j.parkreldis.2011.03.005
  • 8 Gerwig M, Krüger S, Kreuz FR, Kreis S, Gizewski ER, Timmann D. Characteristic MRI and funduscopic findings help diagnose ARSACS outside Quebec. Neurology. 2010;75(23):2133. https://doi.org/10.1212/WNL.0b013e318200d7f8
  • 9 Richter AM, Ozgul RK, Poisson VC, Topaloglu H. Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey. Neurogenetics. 2004;5(3):165-70. https://doi.org/10.1007/s10048-004-0179-y
  • 10 Grieco GS, Malandrini A, Comanducci G, Leuzzi V, Valoppi M, Tessa A et al. Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay type. Neurology. 2004;62(1):103-6. https://doi.org/10.1212/01.WNL.0000104491.66816.77
  • 11 Criscuolo C, Saccà F, De Michele G, Mancini P, Combarros O, Infante J et al. Novel mutation of SACS gene in a Spanish family with autosomal recessive spastic ataxia. Mov Disord. 2005;20(10):1358-61. https://doi.org/10.1002/mds.20579
  • 12 Bouhlal Y, El Euch-Fayeche G, Hentati F, Amouri R. A novel SACS gene mutation in a Tunisian family. J Mol Neurosci. 2009;39(3):333-6. https://doi.org/10.1007/s12031-009-9212-9
  • 13 Takiyama Y. Autosomal recessive spastic ataxia of Charlevoix-Saguenay. Neuropathology. 2006;26(4):368-35. https://doi.org/10.1111/j.1440-1789.2006.00664.x
  • 14 Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM et al. ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia. Neurogenetics. 2008;9(3):207-14. https://doi.org/10.1007/s10048-008-0131-7
  • 15 Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K et al. Mutations in SACS cause atypical and late-onset forms of ARSACS. Neurology. 2010;75(13):1181-8. https://doi.org/10.1212/WNL.0b013e3181f4d86c
  • 16 Martin MH, Bouchard JP, Sylvain M, St-Onge O, Truchon S. Autosomal recessive spastic ataxia of Charlevoix-Saguenay: a report of MR imaging in 5 patients. AJNR Am J Neuroradiol. 2007;28(8):1606-8. https://doi.org/10.3174/ajnr.A0603
  • 17 Shimazaki H, Takiyama Y, Honda J, Sakoe K, Namekawa M, Tsugawa J et al. Middle cerebellar peduncles and Pontine T2 hypointensities in ARSACS. J Neuroimaging. 2013;23(1):82-5. https://doi.org/10.1111/j.1552-6569.2011.00647.x
  • 18 Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24. https://doi.org/10.1038/gim.2015.30
  • 19 De Braekeleer M, Giasson F, Mathieu J, Roy M, Bouchard JP, Morgan K. Genetic epidemiology of autosomal recessive spastic ataxia of Charlevoix-Saguenay in northeastern Quebec. Genet Epidemiol. 1993;10(1):17-25. https://doi.org/10.1002/gepi.1370100103
  • 20 Thiffault I, Dicaire MJ, Tetreault M, Huang KN, Demers-Lamarche J, Bernard G et al. Diversity of ARSACS mutations in French-Canadians. Can J Neurol Sci. 2013;40(1):61-6. https://doi.org/10.1017/S0317167100012968
  • 21 Hara K, Onodera O, Endo M, Kondo H, Shiota H, Miki K et al. Sacsin-related autosomal recessive ataxia without prominent retinal myelinated fibers in Japan. Mov Disord. 2005;20(3):380-2. https://doi.org/10.1002/mds.20315
  • 22 Vingolo EM, Di Fabio R, Salvatore S, Grieco G, Bertini E, Leuzzi V et al. Myelinated retinal fibers in autosomal recessive spastic ataxia of Charlevoix-Saguenay. Eur J Neurol. 2011;18(9):1187-90. https://doi.org/10.1111/j.1468-1331.2010.03335.x
  • 23 Desserre J, Devos D, Sautière BG, Debruyne P, Santorelli FM, Vuillaume I et al. Thickening of peripapillar retinal fibers for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay. Cerebellum. 2011;10(4):758-62. https://doi.org/10.1007/s12311-011-0286-x
  • 24 Synofzik M, Soehn AS, Gburek-Augustat J, Schicks J, Karle KN, Schüle R et al. Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS): expanding the genetic, clinical and imaging spectrum. Orphanet J Rare Dis. 2013;8(1):41-53. https://doi.org/10.1186/1750-1172-8-41
  • 25 Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N et al. New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay. Ann Neurol. 2015;78(6):871-86. https://doi.org/10.1002/ana.24509
  • 26 Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S et al. Hereditary spastic paraplegia: clinicogenetic lessons from 608 patients. Ann Neurol. 2016;79(4):646-58. https://doi.org/10.1002/ana.24611
  • 27 Pedroso JL, Braga-Neto P, Abrahão A, Rivero RL, Abdalla C, Abdala N et al. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): typical clinical and neuroimaging features in a Brazilian family. Arq Neuropsiquiatr. 2011;69(2B):288-91. https://doi.org/10.1590/S0004-282X2011000300004
  • 28 Anheim M, Tranchant C, Koenig M. The autosomal recessive cerebellar ataxias. N Engl J Med. 2012;366(7):636-46. https://doi.org/10.1056/NEJMra1006610