Genetic prion disease with codon 196 PRNP mutation: clinical and pathological findings

Ten percent to 15% of all human transmissible spongiform encephalopathy are characterized by a mutation in prion protein gene (PRNP). They are distinct with respect to clinical signs, disease onset, disease duration, and diagnostic findings. During our surveillance activities in Germany, we identified 7 patients with the rare mutation E196K in PRNP gene, thereof 4 patients belonging to 2 families. The clinical syndromes were characterized by nonspecific and psychiatric symptoms at disease onset and progressed to predominant motor signs. These patients showed a late median disease onset of 71 years and short disease duration of 6.5 months. In absence of family history, they mimicked sporadic Creutzfeldt-Jakob disease (CJD). In clinical tests they were 100% positive for 14-3-3 protein detection in cerebrospinal fluid and less sensitive for magnetic resonance imaging (MRI) and electroencephalogram (EEG) abnormalities. As a secondary magnetic resonance imaging (MRI) abnormality, we have seen conspicuous common involvement of the subcortical white matter in 57%. Four patients underwent autopsy-pathological lesions revealed striking similarity to sporadic Creutzfeldt-Jakob disease but also involvement of the white matter.