Variably Protease-Sensitive Prionopathy (VPSPr)

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 (PrP^Sc). 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 PrP^Sc 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.