Prion diseases are under compulsory notification in Brazil: Surveillance of cases evaluated by biochemical and/or genetic markers from 2005 to 2007

Martins, Vilma Regina; Gomes, Hélio Rodrigues; Chimelli, Leila; Rosemberg, Sergio; Landemberger, Michele Christine

doi:10.1590/S1980-57642008DN10400004

Abstract

The emergence of the new variant of Creutzfeldt-Jakob disease (vCJD) in the United Kingdom has raised concerns over the risks of this prion disease in other parts of the world. Since 2005, human prion diseases have been under compulsory notification in Brazil. It is well known that some polymorphisms within the cellular prion gene (PRNP) have been associated to a higher susceptibility to sporadic CJD (sCJD) and vCJD. Objectives: To describe the first notified cases and to evaluate the presence of mutations and polymorphisms of the PRNP in these cases. Methods: Thirty-five notified cases were evaluated by clinical, auxiliary exams and biochemical and/or genetic tests and classified according to the World Health Organization criteria for CJD. A control group (N=202) was included for the purpose of comparing the genetic analyses. Results: Twenty seven cases (74%) were classified as possible sCJD while 51% fulfilled the criteria for probable sCJD. Brain tissue analysis was available in three cases, where two were classified as definite sCJD and one as unconfirmed sCJD. Mutation of the PRNP was not found, and regarding the codon 129 polymorphism, valine in both alleles (Val129Val) was more frequent in patients than in the control group (OR=4.98; 1.55-15.96; p=0.007) when all possible cases were included, but not when only probable cases were considered. Conclusions: Our data did not show correlation of PRNP polymorphisms with probable sCJD cases. It is necessary to work toward notification of all cases of possible CJD in Brazil and to increase the rate of definitive diagnoses.

Key words:
prion; prion diseases; transmissible spongiform encephalopathy; Creutzfeldt-Jakob disease; genetic polymorphism

Resumo

O aparecimento da nova variante da doença de Creutzfeldt-Jakob (vDCJ) na Grã-Bretanha causou preocupações quanto aos riscos de doenças por príons em outras partes do globo. Desde 2005, doenças humanas por príons são de notificação compulsória no Brasil. É bem conhecido que alguns polimorfismos do gene da proteína príon celular (PRNP) têm sido associados a maior susceptibilidade a DCJ esporádica (DCJe) e a vDCJ. Objetivos: Descrever os primeiros casos notificados e avaliar a presença de mutações e polimorfismos do PRNP nesses casos. Métodos: 35 casos notificados foram avaliados clinicamente, mediante exames complementares, testes bioquímicos e/ou genéticos e classificados de acordo com os critérios de DCJ da Organização Mundial de Saúde. Grupo controle (N=202) foi incluído para comparação dos dados da análise genética. Resultados: 27 casos (74%) foram classificados como possível DCJe, dos quais 51% preencheram critérios para provável DCJe. Exame neuropatológico do encéfalo foi realizado em apenas 3 casos, dos quais 2 foram classificados como DCJe definida e um como DCJe não confirmada. Mutações do PRNP não foram encontradas e, com respeito ao polimorfismo do códon 129, valina em ambos os alelos (Val129Val) foi mais freqüente em pacientes do que em controles (OR=4,98; 1,55-15,96; p=0,007) quando todos os casos foram investigados, mas não quando apenas casos prováveis foram incluídos. Conclusões: Nossos dados não mostram correlação dos polimorfismos do PRNP com provável DCJe. É necessário ampliar a notificação de todos os casos de possível DCJ no Brasil e o diagnóstico definitivo.

Palavras-chave:
prion; doenças por prions; encefalopatias espongiformes transmissíveis; doença de Creutzfeldt-Jakob; polimorfismo genético

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References

¹
Prusiner SB. Prions. Proc Natl Acad Sci USA 1998;95:13363-13383.
²
Weissmann C, Aguzzi A. Perspectives: neurobiology. PrP's double causes trouble. Science 1999;286:914-915.
³
Prusiner SB, McKinley MP, Bowman KA, et al. Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 1983;35:349-358.
⁴
Bueler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie. Cell 1993;73:1339-1347.
⁵
Collins SJ, Lawson VA, Masters CL. Transmissible spongiform encephalopathies. Lancet 2004;363(9402):51-61.
⁶
Swerdlow AJ, Higgins CD, Adlard P, Jones ME, Preece MA. Creutzfeldt-Jakob disease in United Kingdom patients treated with human pituitary growth hormone. Neurology 2003;61:783-791.
⁷
Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1977;1(8009):478-479.
⁸
Heckmann JG, Lang CJ, Petruch F, et al. Transmission of Creutzfeldt-Jakob disease via a corneal transplant. J Neurol Neurosurg Psychiatry 1997;63:388-390.
⁹
Duffy P, Wolf J, Collins G, DeVoe AG, Streeten B, Cowen D. Letter: Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974;290:692-693.
¹⁰
Hogan RN, Cavanagh HD. Transplantation of corneal tissue from donors with diseases of the central nervous system. Cornea 1995;14:547-553.
¹¹
Heath CA, Barker RA, Esmonde TF, et al. Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK. J Neurol Neurosurg Psychiatry 2006;77:880-882.
¹²
Noguchi-Shinohara M, Hamaguchi T, Kitamoto T, et al. Clinical features and diagnosis of dura mater graft associated Creutzfeldt Jakob disease. Neurology 2007;69:360-367.
¹³
Brown P, Brandel JP, Preece M, Sato T. Iatrogenic Creutzfeldt-Jakob disease: the waning of an era. Neurology 2006;67:389-393.
¹⁴
Blattler T. Implications of prion diseases for neurosurgery. Neurosurg Rev 2002;25:195-203.
¹⁵
Ladogana A, Puopolo M, Croes EA, et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology 2005;64:1586-1591.
¹⁶
Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347(9006):921-925.
¹⁷
Bruce ME, Will RG, Ironside JW, McConnell I, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997;389:498-501.
¹⁸
Bradley R, Collee JG, Liberski PP. Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 1. Folia Neuropathol 2006;44:93-101.
¹⁹
Collee JG, Bradley R, Liberski PP. Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 2. Folia Neuropathol 2006;44:102-110.
²⁰
Bishop MT, Hart P, Aitchison L, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006;5:393-398.
²¹
Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Three reported cases of variant Creutzfeldt-Jakob disease transmission following transfusion of labile blood components. Vox Sang 2006;91:348.
²²
Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study. Vox Sang 2006;91:221-230.
²³
Llewelyn CA, Hewitt PE, Knight RS, et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004;363(9407):417-421.
²⁴
Wroe SJ, Pal S, Siddique D, et al. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 2006;368(9552):2061-2067.
²⁵
Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004;364 (9433):527-529.
²⁶
Gattás VL, Lima-Neto AS, Dimech GS, et al. New Variant of Creutzfeld-Jakob (nvCJD) disease and other human prion disease under epidemiological surveillance. Dement Neuropsychol 2007;1(4):339-346.
²⁷
Huang N, Marie SK, Livramento JA, Chammas R, Nitrini R. 14-3-3 protein in the CSF of patients with rapidly progressive dementia. Neurology 2003; 61:354-357.
²⁸
Castro RM, Landemberger MC, Walz R, et al. High capacity and low cost detection of prion protein gene variant alleles by denaturing HPLC. J Neurosci Methods 2004;139:263-269.
²⁹
Hsich G, Kenney K, Gibbs CJ, Lee KH, Harrington MG. The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 1996;335:924-930.
³⁰
Will RG, Matthews WB. A retrospective study of Creutzfeldt-Jakob disease in England and Wales 1970-79. I: Clinical features. J Neurol Neurosurg Psychiatry 1984;47:134-140.
³¹
Shiga Y, Miyazawa K, Sato S, et al. Diffusion-weighted MRI abnormalities as an early diagnostic marker for Creutzfeldt-Jakob disease. Neurology 2004;63:443-449.
³²
Zeidler M, Johnstone EC, Bamber RW, et al. New variant Creutzfeldt-Jakob disease: psychiatric features. Lancet 1997;350(9082):908-910.
³³
Macleod MA, Stewart GE, Zeidler M, Will R, Knight R. Sensory features of variant Creutzfeldt-Jakob disease. J Neurol 2002;249:706-711.
³⁴
Zeidler M, Sellar RJ, Collie DA, et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 2000; 355(9213):1412-1418.
³⁵
Deslys JP, Marce D, Dormont D. Similar genetic susceptibility in iatrogenic and sporadic Creutzfeldt-Jakob disease. J Gen Virol 1994;75(Pt 1):23-27.
³⁶
Windl O, Dempster M, Estibeiro JP, et al. Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum Genet 1996;98:259-264.
³⁷
Hill AF, Butterworth RJ, Joiner S, et.al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999; 353(9148):183-189.

Publication Dates

Publication in this collection
Oct-Dec 2007

History

Received
18 Oct 2007
Reviewed
05 Nov 2007
Accepted
20 Nov 2007

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Prusiner SB. Prions. Proc Natl Acad Sci USA 1998;95:13363-13383.

[2] ²
Weissmann C, Aguzzi A. Perspectives: neurobiology. PrP's double causes trouble. Science 1999;286:914-915.

[3] ³
Prusiner SB, McKinley MP, Bowman KA, et al. Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 1983;35:349-358.

[4] ⁴
Bueler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie. Cell 1993;73:1339-1347.

[5] ⁵
Collins SJ, Lawson VA, Masters CL. Transmissible spongiform encephalopathies. Lancet 2004;363(9402):51-61.

[6] ⁶
Swerdlow AJ, Higgins CD, Adlard P, Jones ME, Preece MA. Creutzfeldt-Jakob disease in United Kingdom patients treated with human pituitary growth hormone. Neurology 2003;61:783-791.

[7] ⁷
Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1977;1(8009):478-479.

[8] ⁸
Heckmann JG, Lang CJ, Petruch F, et al. Transmission of Creutzfeldt-Jakob disease via a corneal transplant. J Neurol Neurosurg Psychiatry 1997;63:388-390.

[9] ⁹
Duffy P, Wolf J, Collins G, DeVoe AG, Streeten B, Cowen D. Letter: Possible person-to-person transmission of Creutzfeldt-Jakob disease. N Engl J Med 1974;290:692-693.

[10] ¹⁰
Hogan RN, Cavanagh HD. Transplantation of corneal tissue from donors with diseases of the central nervous system. Cornea 1995;14:547-553.

[11] ¹¹
Heath CA, Barker RA, Esmonde TF, et al. Dura mater-associated Creutzfeldt-Jakob disease: experience from surveillance in the UK. J Neurol Neurosurg Psychiatry 2006;77:880-882.

[12] ¹²
Noguchi-Shinohara M, Hamaguchi T, Kitamoto T, et al. Clinical features and diagnosis of dura mater graft associated Creutzfeldt Jakob disease. Neurology 2007;69:360-367.

[13] ¹³
Brown P, Brandel JP, Preece M, Sato T. Iatrogenic Creutzfeldt-Jakob disease: the waning of an era. Neurology 2006;67:389-393.

[14] ¹⁴
Blattler T. Implications of prion diseases for neurosurgery. Neurosurg Rev 2002;25:195-203.

[15] ¹⁵
Ladogana A, Puopolo M, Croes EA, et al. Mortality from Creutzfeldt-Jakob disease and related disorders in Europe, Australia, and Canada. Neurology 2005;64:1586-1591.

[16] ¹⁶
Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996;347(9006):921-925.

[17] ¹⁷
Bruce ME, Will RG, Ironside JW, McConnell I, et al. Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997;389:498-501.

[18] ¹⁸
Bradley R, Collee JG, Liberski PP. Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 1. Folia Neuropathol 2006;44:93-101.

[19] ¹⁹
Collee JG, Bradley R, Liberski PP. Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 2. Folia Neuropathol 2006;44:102-110.

[20] ²⁰
Bishop MT, Hart P, Aitchison L, et al. Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol 2006;5:393-398.

[21] ²¹
Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Three reported cases of variant Creutzfeldt-Jakob disease transmission following transfusion of labile blood components. Vox Sang 2006;91:348.

[22] ²²
Hewitt PE, Llewelyn CA, Mackenzie J, Will RG. Creutzfeldt-Jakob disease and blood transfusion: results of the UK Transfusion Medicine Epidemiological Review study. Vox Sang 2006;91:221-230.

[23] ²³
Llewelyn CA, Hewitt PE, Knight RS, et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004;363(9407):417-421.

[24] ²⁴
Wroe SJ, Pal S, Siddique D, et al. Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. Lancet 2006;368(9552):2061-2067.

[25] ²⁵
Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004;364 (9433):527-529.

[26] ²⁶
Gattás VL, Lima-Neto AS, Dimech GS, et al. New Variant of Creutzfeld-Jakob (nvCJD) disease and other human prion disease under epidemiological surveillance. Dement Neuropsychol 2007;1(4):339-346.

[27] ²⁷
Huang N, Marie SK, Livramento JA, Chammas R, Nitrini R. 14-3-3 protein in the CSF of patients with rapidly progressive dementia. Neurology 2003; 61:354-357.

[28] ²⁸
Castro RM, Landemberger MC, Walz R, et al. High capacity and low cost detection of prion protein gene variant alleles by denaturing HPLC. J Neurosci Methods 2004;139:263-269.

[29] ²⁹
Hsich G, Kenney K, Gibbs CJ, Lee KH, Harrington MG. The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies. N Engl J Med 1996;335:924-930.

[30] ³⁰
Will RG, Matthews WB. A retrospective study of Creutzfeldt-Jakob disease in England and Wales 1970-79. I: Clinical features. J Neurol Neurosurg Psychiatry 1984;47:134-140.

[31] ³¹
Shiga Y, Miyazawa K, Sato S, et al. Diffusion-weighted MRI abnormalities as an early diagnostic marker for Creutzfeldt-Jakob disease. Neurology 2004;63:443-449.

[32] ³²
Zeidler M, Johnstone EC, Bamber RW, et al. New variant Creutzfeldt-Jakob disease: psychiatric features. Lancet 1997;350(9082):908-910.

[33] ³³
Macleod MA, Stewart GE, Zeidler M, Will R, Knight R. Sensory features of variant Creutzfeldt-Jakob disease. J Neurol 2002;249:706-711.

[34] ³⁴
Zeidler M, Sellar RJ, Collie DA, et al. The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease. Lancet 2000; 355(9213):1412-1418.

[35] ³⁵
Deslys JP, Marce D, Dormont D. Similar genetic susceptibility in iatrogenic and sporadic Creutzfeldt-Jakob disease. J Gen Virol 1994;75(Pt 1):23-27.

[36] ³⁶
Windl O, Dempster M, Estibeiro JP, et al. Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum Genet 1996;98:259-264.

[37] ³⁷
Hill AF, Butterworth RJ, Joiner S, et.al. Investigation of variant Creutzfeldt-Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 1999; 353(9148):183-189.

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