ABSTRACT
An atypical case of prion disease is described in a 54-year-old Dutch man, homozygous for valine at codon 129 of the prion protein gene (PRNP). The clinical phenotype was characterised by progressive dementia, spastic paraplegia and sensorimotor polyneuropathy. The disease duration was 20 months. Genetic analysis of PRNP did not reveal any abnormalities. Neuropathologically, only mild spongiform change and a coarse granular immunohistochemical staining for the abnormal prion protein, PrP(Sc), was observed, with poorly formed plaques in the molecular layer of the cerebellar cortex. However, Western blotting showed low but detectable levels of proteinase K(PK)-resistant PrP(Sc) occurring in an unusual ladder-like profile. These features define a phenotype that corresponds to the recently described protease-sensitive prionopathy (PSPr). Our report on the first Dutch patient with PSPr further expands the spectrum of prionopathies and exemplifies the need to re-evaluate cases of atypical prion disease.
Subject(s)
Gerstmann-Straussler-Scheinker Disease/diagnosis , Gerstmann-Straussler-Scheinker Disease/genetics , PrPSc Proteins/metabolism , Prions/genetics , Brain/metabolism , Brain/pathology , Endopeptidase K/metabolism , Gerstmann-Straussler-Scheinker Disease/enzymology , Gerstmann-Straussler-Scheinker Disease/pathology , Homozygote , Humans , Male , Netherlands , Phenotype , Polymorphism, Genetic , Prion ProteinsSubject(s)
Brain/pathology , Prion Diseases/diagnosis , Prion Diseases/pathology , Blotting, Western , Brain/metabolism , Creutzfeldt-Jakob Syndrome/diagnosis , Creutzfeldt-Jakob Syndrome/metabolism , Creutzfeldt-Jakob Syndrome/pathology , Diagnosis, Differential , Fatal Outcome , Female , Humans , Immunohistochemistry , Middle Aged , Prion Diseases/metabolism , United KingdomSubject(s)
Blood Donors , Blood Transfusion , Brain/pathology , Creutzfeldt-Jakob Syndrome/pathology , Creutzfeldt-Jakob Syndrome/transmission , Blotting, Western , Brain/metabolism , Cerebellum/metabolism , Cerebellum/pathology , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , Creutzfeldt-Jakob Syndrome/metabolism , Humans , Immunohistochemistry , Middle Aged , Prions/metabolism , Young AdultABSTRACT
BACKGROUND: Involvement of the eye has been reported in patients with variant Creutzfeldt-Jakob disease (vCJD), but there is disagreement on whether retinal involvement occurs in sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: Western blotting, paraffin embedded tissue blotting, and immunohistochemistry were used to test whether the abnormal form of the prion protein (PrPSc) accumulates to detectable levels in the eye in a case of the most common subtype of sCJD (MM1). RESULTS: Low levels of PrPSc were detectable in the retina, localised to the plexiform layers of the central retina. PrPSc was not detectable in other ocular tissues. CONCLUSIONS: The abnormal form of the prion protein is present in the retina in the most common sCJD subtype (MM1), albeit at levels lower than those found previously in vCJD and in sCJD of the VV2 subtype.
