Neurological Sciences

, Volume 30, Issue 5, pp 417–420 | Cite as

Creutzfeldt–Jakob disease with E200K PRNP mutation: a case report and revision of the literature

  • Michelangelo Mancuso
  • Gabriele Siciliano
  • Sabina Capellari
  • Daniele Orsucci
  • Policarpo Moretti
  • Giuseppe Di Fede
  • Silvia Suardi
  • Rosaria Strammiello
  • Piero Parchi
  • Fabrizio Tagliavini
  • Luigi Murri
Case Report

Abstract

Creutzfeldt–Jakob disease (CJD) is typically characterized by rapidly progressive dementia and myoclonus, and it is caused by a conformational change of the prion protein. The heritable forms are associated with mutation in the gene encoding the prion protein (PRNP). We report a 63-year-old Italian woman harboring the E200K PRNP mutation. Electroencephalogram, cerebrospinal fluid analysis, PRNP gene sequencing, histopathologic examination, immunohistochemical studies, and Western blotting analysis confirmed the diagnosis of CJD. Pyramidal involvement was the first sign and the prominent clinical feature. Later on, she developed also myoclonus, ataxia, spastic tetraplegia, and at last dementia with akinetic mutism. Usually, signs of degeneration of the pyramidal tracts occur in a small number of patients as the disease advances. Our report supports the variability of the clinical expression of the E200K genetic CJD. Further studies are needed to understand the molecular basis underlying the phenotypic variability among patients carrying this mutation.

Keywords

CJD Codon 200 Prions PrP PRNP Spastic tetraparesis 

References

  1. 1.
    Prusiner SB (2001) Shattuck lecture—neurodegenerative diseases and prions. N Engl J Med 344:1516PubMedCrossRefGoogle Scholar
  2. 2.
    Mead S (2006) Prion disease genetics. Eur J Hum Genet 14:273–281PubMedCrossRefGoogle Scholar
  3. 3.
    Ladogana A, Puopolo M, Poleggi A et al (2005) High incidence of genetic human transmissible spongiform encephalopathies in Italy. Neurology 64:1592–1597PubMedCrossRefGoogle Scholar
  4. 4.
    Gambetti P, Kong Q, Zou W et al (2003) Sporadic and familial CJD: classification and characterisation. Br Med Bull 66:213–239PubMedCrossRefGoogle Scholar
  5. 5.
    Kovács GG, Puopolo M, Ladogana A et al (2005) Genetic prion disease: the EUROCJD experience. Hum Genet 118:166–174PubMedCrossRefGoogle Scholar
  6. 6.
    Monari L, Chen SG, Brown P et al (1994) Fatal familial insomnia and familial Creutzfeldt–Jakob disease: different prion proteins determined by a DNA polymorphism. Proc Natl Acad Sci USA 91:2839–2842PubMedCrossRefGoogle Scholar
  7. 7.
    Parchi P, Capellari S, Chen SG et al (1997) Typing prion isoforms. Nature 386:232–234PubMedCrossRefGoogle Scholar
  8. 8.
    Heinemann U, Krasnianski A, Meissner B et al (2007) Creutzfeldt–Jakob disease in Germany: a prospective 12-year surveillance. Brain 130:1350–1359PubMedCrossRefGoogle Scholar
  9. 9.
    Goldfarb LG, Mitrová E, Brown P et al (1990) Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt–Jakob disease in Slovakia. Lancet 336:514–515PubMedCrossRefGoogle Scholar
  10. 10.
    Korczyn AD, Chapman J, Goldfarb LG et al (1991) A mutation in the prion protein gene in Creutzfeldt–Jakob disease in Jewish patients of Libyan, Greek, and Tunisian origin. Ann N Y Acad Sci 640:171–176PubMedGoogle Scholar
  11. 11.
    Meiner Z, Gabizon R, Prusiner SB (1997) Familial Creutzfeldt–Jakob disease. Codon 200 prion disease in Libyan Jews. Medicine (Baltimore) 76(22):7–237Google Scholar
  12. 12.
    Lee HS, Sambuughin N, Cervenakova L et al (1999) Ancestral origins and worldwide distribution of the PRNP 200K mutation causing familial Creutzfeldt–Jakob disease. Am J Hum Genet 64:1063–1070PubMedCrossRefGoogle Scholar
  13. 13.
    Goldfarb LG, Brown P, Mitrovà E et al (1991) Creutzfeldt–Jacob disease associated with the PRNP codon 200Lys mutation: an analysis of 45 families. Eur J Epidemiol 7:477–486PubMedCrossRefGoogle Scholar
  14. 14.
    Mitrova E, Belay G (2002) Creutzfeldt–Jakob disease with E200K mutation in Slovakia: characterization and development. Acta Virol 46:31–39PubMedGoogle Scholar
  15. 15.
    Chapman J, Ben-Israel J, Goldhammer Y et al (1994) The risk of developing Creutzfeldt–Jakob disease in subjects with the PRNP gene codon 200 point mutation. Neurology 44:1683–1686PubMedGoogle Scholar
  16. 16.
    D’Alessandro M, Petraroli R, Ladogana A et al (1998) High incidence of Creutzfeldt–Jakob disease in rural Calabria, Italy. Lancet 352:1989–1990PubMedCrossRefGoogle Scholar
  17. 17.
    Jarius C, Kovacs GG, Belay G et al (2003) Distinctive cerebellar immunoreactivity for the prion protein in familial (E200K) Creutzfeldt–Jakob disease. Acta Neuropathol (Berl) 105:449–454Google Scholar
  18. 18.
    Chapman J, Brown P, Rabey JM et al (1992) Transmission of spongiform encephalopathy from a familial Creutzfeldt–Jakob disease patient of Jewish Libyan origin carrying the PRNP codon 200 mutation. Neurology 42:1249–1250PubMedGoogle Scholar
  19. 19.
    Brown P, Gálvez S, Goldfarb LG et al (1992) Familial Creutzfeldt–Jakob disease in Chile is associated with the codon 200 mutation of the PRNP amyloid precursor gene on chromosome 20. J Neurol Sci 112:65–67PubMedCrossRefGoogle Scholar
  20. 20.
    Collinge J, Palmer MS, Campbell TA et al (1993) Inherited prion disease (PrP lysine 200) in Britain: two case reports. BMJ 306:301–302PubMedCrossRefGoogle Scholar
  21. 21.
    Inoue I, Kitamoto T, Doh-ura K et al (1994) Japanese family with Creutzfeldt–Jakob disease with codon 200 point mutation of the prion protein gene. Neurology 44:299–301PubMedGoogle Scholar
  22. 22.
    Salvatore M, Pocchiari M, Cardone F et al (1996) Codon 200 mutation in a new family of Chilean origin with Creutzfeldt–Jakob disease. J Neurol Neurosurg Psychiatry 61:111–112PubMedCrossRefGoogle Scholar
  23. 23.
    Miyakawa T, Inoue K, Iseki E et al (1998) Japanese Creutzfeldt–Jakob disease patients exhibiting high incidence of the E200K PRNP mutation and located in the basin of a river. Neurol Res 20:684–688PubMedGoogle Scholar
  24. 24.
    Windl O, Giese A, Schulz-Schaeffer W et al (1999) Molecular genetics of human prion diseases in Germany. Hum Genet 105:244–252PubMedCrossRefGoogle Scholar
  25. 25.
    Chapman J, Brown P, Goldfarb LG et al (1993) Clinical heterogeneity and unusual presentations of Creutzfeldt–Jakob disease in Jewish patients with the PRNP codon 200 mutation. J Neurol Neurosurg Psychiatry 56:1109–1112PubMedCrossRefGoogle Scholar
  26. 26.
    Bertoni JM, Brown P, Goldfarb LG et al (1992) Familial Creutzfeldt–Jakob disease (codon 200 mutation) with supranuclear palsy. JAMA 268:2413–2415PubMedCrossRefGoogle Scholar
  27. 27.
    Chapman J, Arlazoroff A, Goldfarb LG et al (1996) Fatal insomnia in a case of familial Creutzfeldt–Jakob disease with the codon 200(Lys) mutation. Neurology 46:758–761PubMedGoogle Scholar
  28. 28.
    Taratuto AL, Piccardo P, Reich EG et al (2002) Insomnia associated with thalamic involvement in E200K Creutzfeldt–Jakob disease. Neurology 58:362–367PubMedGoogle Scholar
  29. 29.
    Antoine JC, Laplanche JL, Mosnier JF et al (1996) Demyelinating peripheral neuropathy with Creutzfeldt–Jakob disease and mutation at codon 200 of the prion protein gene. Neurology 46:1123–1127PubMedGoogle Scholar
  30. 30.
    Hellmann MA, Melamed E (2002) Focal dystonia as the presenting sign in Creutzfeldt–Jakob disease. Mov Disord 17:1097–1098PubMedCrossRefGoogle Scholar
  31. 31.
    Konno S, Murata M, Toda T et al (2008) Familial Creutzfeldt–Jakob Disease with a codon 200 mutation presenting as thalamic syndrome: diagnosis by single photon emission computed tomography using (99m)Tc-ethyl cysteinate dimer. Intern Med 47:65–67PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Michelangelo Mancuso
    • 1
  • Gabriele Siciliano
    • 1
  • Sabina Capellari
    • 2
  • Daniele Orsucci
    • 1
  • Policarpo Moretti
    • 1
  • Giuseppe Di Fede
    • 3
  • Silvia Suardi
    • 3
  • Rosaria Strammiello
    • 2
  • Piero Parchi
    • 2
  • Fabrizio Tagliavini
    • 3
  • Luigi Murri
    • 1
  1. 1.Department of Neuroscience, Neurological ClinicUniversity of PisaPisaItaly
  2. 2.Department of Neurological ScienceUniversity of BolognaBolognaItaly
  3. 3.“C. Besta” National Neurological InstituteVia Celoria 11Italy

Personalised recommendations