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Coexistence of protease sensitive and resistant prion protein in 129VV homozygous sporadic Creutzfeldt–Jakob disease: a case report

Ana B Rodríguez-Martínez1, Adolfo López de Munain24, Isidro Ferrer34, Juan J Zarranz5, Begoña Atarés6, Nuria T Villagra6, Jose M Arteagoitia7, Joseba M Garrido1 and Ramón A Juste1*

Author Affiliations

1 Department of Animal Health, Neiker-Tecnalia, Berreaga 1, Derio, Bizkaia, 48160, Spain

2 Neurology Service, Hospital de Donosti, San Sebastian, Spain

3 Institute of Neuropathology, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain

4 CIBERNED, Instituto de Salud Carlos III, Barcelona, Spain

5 Neurology Service, Hospital de Cruces, Plaza Cruces-Gurutzeta 12, Barakaldo, Bizkaia, 48902, Spain

6 Pathology Service, Hospital de Txagorritxu, José Achótegui s/n. 01009, Vitoria-Gasteiz, Alava, Spain

7 Department of Health and Consumption, Gobierno Vasco, Vitoria-Gasteiz, Alava, Spain

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Journal of Medical Case Reports 2012, 6:348  doi:10.1186/1752-1947-6-348

Published: 11 October 2012

Abstract

Introduction

The coexistence of different molecular types of classical protease-resistant prion protein in the same individual have been described, however, the simultaneous finding of these with the recently described protease-sensitive variant or variably protease-sensitive prionopathy has, to the best of our knowledge, not yet been reported.

Case presentation

A 74-year-old Caucasian woman showed a sporadic Creutzfeldt–Jakob disease clinical phenotype with reactive depression, followed by cognitive impairment, akinetic-rigid Parkinsonism with pseudobulbar syndrome and gait impairment with motor apraxia, visuospatial disorientation, and evident frontal dysfunction features such as grasping, palmomental reflex and brisk perioral reflexes. She died at age 77.

Neuropathological findings showed: spongiform change in the patient’s cerebral cortex, striatum, thalamus and molecular layer of the cerebellum with proteinase K-sensitive synaptic-like, dot-like or target-like prion protein deposition in the cortex, thalamus and striatum; proteinase K-resistant prion protein in the same regions; and elongated plaque-like proteinase K-resistant prion protein in the molecular layer of the cerebellum. Molecular analysis of prion protein after proteinase K digestion revealed decreased signal intensity in immunoblot, a ladder-like protein pattern, and a 71% reduction of PrPSc signal relative to non-digested material. Her cerebellum showed a 2A prion protein type largely resistant to proteinase K. Genotype of polymorphism at codon 129 was valine homozygous.

Conclusion

Molecular typing of prion protein along with clinical and neuropathological data revealed, to the best of our knowledge, the first case of the coexistence of different protease-sensitive prion proteins in the same patient in a rare case that did not fulfill the current clinical diagnostic criteria for either probable or possible sporadic Creutzfeldt–Jakob disease. This highlights the importance of molecular analyses of several brain regions in order to correctly diagnose rare and atypical prionopathies.

Keywords:
Creutzfeldt–Jakob; Prion; Protease resistance; Resistant PrP; Sensitive PrP; Variably Protease Sensitive Prionopathy