Sporadic, acquired, and genetic human
prion diseases are characterized neuropathologically by distinct deposition patterns of the abnormal, disease-associated form of the
prion protein (PrP(sc)). In addition to mutations in the
prion protein gene (PRNP), PrP(sc) immunostaining patterns correlate with molecular phenotypes of
prion diseases defined by the PRNP polymorphism at
codon 129 and with
protease-resistant PrP classified by Western blotting. Some point or insertional PRNP mutations share similar clinical and neuropathological phenotypes, whereas others show great variability even within the same family. Here we report a patient who presented clinically as
sporadic Creutzfeldt-Jakob disease (CJD). Histologically moderate spongiform change was seen in cerebral and cerebellar cortical areas. Neuronal loss was restricted mainly to the occipital cortex and the basal ganglia. Surprisingly, numerous eosinophilic globular structures were noted in the molecular layer and the parahippocampal gyrus. These globules showed intense PrP immunopositivity using anti-PrP
antibodies against different
epitopes. They were stained with PAS but lacked congophilia and birefringence in polarized light. Ultrastructurally, globules were composed of 21-nm-thick intermingled filaments without dense core. Genetic analysis revealed a PRNP 144 base pair insertion. Our case reinforces the importance of molecular genetic diagnosis, especially in those patients who lack a family history of
prion disease and show unusual neuropathological changes. It also widens the phenotypic spectrum of
prion diseases. The phenotypic variability within the same mutation suggests further, yet uncharacterized, genetic or epigenetic influence on phenotype in these diseases.