Sporadic Creutzfeldt-Jakob Disease in a Very Young Person.

BACKGROUND AND OBJECTIVES: Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of human prion disease and typically occurs in middle to late life. sCJD in early adulthood is extremely uncommon. The purpose of this report is to raise awareness of cases of sCJD in young patients that are not associated with a genetic mutation or acquired prion disease risk factors. METHODS: We describe the clinical presentation, diagnostic workup, and postmortem examination of a 22-year-old man with sCJD. RESULTS: The patient presented with a rapidly progressive neurocognitive disorder consisting of early and prominent psychiatric symptoms. CSF real-time quaking-induced conversion (RT-QuIC) was indeterminate, and brain MRI was suggestive of prion disease. Neuropathologic examination and the absence of a genetic mutation and acquired prion disease risk factors resulted in a final diagnosis of sCJD. CONCLUSION: Although extremely rare, sCJD can occur in young people and should be considered in the setting of rapidly progressive neuropsychiatric conditions. Postmortem examination is required to diagnose the type of prion disease and remains important to surveil for known and potentially novel acquired prion diseases.

Case Report: Histopathology and Prion Protein Molecular Properties in Inherited Prion Disease With a De Novo Seven-Octapeptide Repeat Insertion.

The insertion of additional 168 base pair containing seven octapeptide repeats in the prion protein (PrP) gene region spanning residues 51-91 is associated with inherited prion disease. In 2008, we reported the clinical features of a novel de novo seven-octapeptide repeat insertion (7-OPRI) mutation coupled with codon 129 methionine (M) homozygosity in the PrP gene of a 19-year-old man presenting with psychosis and atypical dementia, and 16-year survival. Here, we describe the histopathological and PrP molecular properties in the autopsied brain of this patient. Histopathological examination revealed widespread brain atrophy, focal spongiform degeneration (SD), cortical PrP plaques, and elongated PrP formations in the cerebellum. Overall, these histopathological features resemble those described in a Belgian pedigree with 7-OPRI mutation except for the presence of PrP plaques in our case, which are morphologically different from the multicore plaques described in some OPRI mutations and in Gerstmann-Sträussler-Scheinker (GSS) syndrome. The comparative characterization of the detergent-soluble and detergent-insoluble PrP in our patient and in sporadic Creutzfeldt-Jakob disease (CJD) revealed distinct molecular signatures. Proteinase K digestion of the pathogenic, disease-associated PrP (PrPD) revealed PrPD type 1 in the cerebral cortex and mixed PrPD types 1 and 2 in the cerebellum. Altogether, the present study outlines the importance of assessing the phenotypical and PrP biochemical properties of these rare conditions, thereby widening the spectrum of the phenotypic heterogeneity of the 7-OPRI insertion mutations. Further studies are needed to determine whether distinct conformers of PrPD are associated with two major clinico-histopathological phenotypes in prion disease with 7-OPRI.

Co-existence of PrPD types 1 and 2 in sporadic Creutzfeldt-Jakob disease of the VV subgroup: phenotypic and prion protein characteristics.

We report a detailed study of a cohort of sporadic Creutzfeldt-Jakob disease (sCJD) VV1-2 type-mixed cases (valine homozygosity at codon 129 of the prion protein, PrP, gene harboring disease-related PrP, PrPD, types 1 and 2). Overall, sCJDVV1-2 subjects showed mixed clinical and histopathological features, which often correlated with the relative amounts of the corresponding PrPD type. However, type-specific phenotypic characteristics were only detected when the amount of the corresponding PrPD type exceeded 20-25%. Overall, original features of types 1 (T1) and 2 (T2) in sCJDVV1 and -VV2, including rostrocaudal relative distribution and conformational indicators, were maintained in sCJDVV1-2 except for one of the two components of T1 identified by electrophoretic mobility as T121. The T121 conformational characteristics shifted in the presence of T2, inferring a conformational effect of PrPD T2 on T121. The prevalence of sCJDVV1-2 was 23% or 57% of all sCJDVV cases, depending on whether standard or highly sensitive type-detecting procedures were adopted. This study, together with previous data from sCJDMM1-2 (methionine homozygosity at PrP gene codon 129) establishes the type-mixed sCJD variants as an important component of sCJD, which cannot be identified with current non-tissue based diagnostic tests of prion disease.