Variably protease-sensitive prionopathy (VPSPr) is a rare sporadic prion disease (identified in 2008).
(See also Overview of Prion Diseases.)
Variably protease-sensitive prionopathy occurs in 1 to 2/100 million people (1).
VPSPr resembles Gerstmann-Sträussler-Scheinker disease (GSS) in terms of the characteristics of the abnormal prion protein (PrPSc). However, unlike in GSS, no mutations in the prion protein gene have been identified.
Clinical manifestations differ from those of Creutzfeldt-Jakob disease, and the PrPSc is less resistant to digestion by proteases; some variants are more sensitive to proteases than others, hence the name: variably protease-sensitive.
Patients present with psychiatric symptoms, speech deficits (aphasia and/or dysarthria), and cognitive impairment. Ataxia and parkinsonism can develop. Average age at onset is 70 years, and duration of survival is 24 months. Approximately 42% of patients have a family history of dementia (1).
Diagnosis of variably protease-sensitive prionopathy is difficult. MRI, EEG, and tests for 14-3-3 protein and tau are usually not helpful, and no mutations have been observed in the coding region of the PRNP gene. CSF RT-QuIC is positive in some cases but is less sensitive in VPSPr than in sCJD.
There is only supportive treatment for VPSPr.
Reference
1. Notari S, Appleby BS, Gambetti P: Variably protease-sensitive prionopathy. Handb Clin Neurol 153:175-190, 2018. doi: 10.1016/B978-0-444-63945-5.00010-6
