Variably protease-sensitive prionopathy (VPSPr)

Families who reach this page have usually been given the name by a neurologist or seen it on a post-mortem report, and found almost nothing written for them. The condition was only recognised in 2008, and the published experience is still small, which is the honest starting point.

What is it?

A prion disease, which means prion protein folding into the wrong shape and building up in the brain, as in CJD and the other conditions in the group. VPSPr was separated out because its abnormal prion protein behaves differently in the laboratory.

The name describes that laboratory difference. In most prion diseases the misfolded protein strongly resists being broken down by enzymes called proteases. In VPSPr it resists less, and by a variable amount, which is what variably protease-sensitive means. It was first reported in 2008 as protease-sensitive prionopathy and renamed in 2010.

How rare is it?

Very. It occurs in about 1 to 2 people in 100 million. An update published in 2013 counted 26 reported cases in total, from the first 11 described.

To put that next to the other forms, sporadic CJD affects about 1 to 2 people in a million each year. How common is prion disease has the comparison.

What does it look like?

The average age at onset is 70. It usually begins with psychiatric symptoms, difficulty with speech, either finding words or forming them, and problems with memory and thinking. Unsteadiness and symptoms resembling Parkinson’s disease can develop later.

Survival is given as about 24 months, which is longer than sporadic CJD. These figures come from small numbers of patients, so they describe the group rather than any individual.

Is it inherited?

No change has been found in PRNP, the prion protein gene, in people with VPSPr. The coding part of the gene has been sequenced in these patients and no mutation has been identified.

A family history of dementia is reported in roughly 42 in every 100 patients, and in the 2013 update 8 of the 26 cases had one. That association is not explained, and dementia is common in older people, so it is not evidence that VPSPr itself is passed on. Anyone worried about a family pattern should talk to a genetic counsellor rather than draw a conclusion from this. Genetic counselling comes first explains how that works.

How is it diagnosed?

With difficulty, and often only after death. MRI, EEG and the spinal fluid markers 14-3-3 and tau, which help in sporadic CJD, are usually not helpful here. The spinal fluid seeding test RT-QuIC is positive in some cases but is less sensitive in VPSPr than in sporadic CJD; in one 2026 comparison 3 of 5 VPSPr samples were positive, which was the smallest improvement of any group in that study.

What identifies it is examination of brain tissue, where the abnormal protein shows a distinctive ladder of bands when a particular antibody is used. How prion disease is diagnosed covers the tests, and the diseases page the wider group.

What treatment and care are there?

Care is supportive: controlling symptoms and supporting the family. No treatment stops the disease. Because the course usually runs over about two years, there is more time than in sporadic CJD to arrange help, and a palliative care team can be involved early rather than at the end.

What to expect covers the practical side of care, and support groups lists people who talk with families, including families with the rarer diagnoses.

Where next?

VPSPr: more detail is the clinical version of this page, and VPSPr for researchers the scientific one. Current trials lists studies with eligibility as the sponsors state it, which for a condition this rare usually means asking whether a study accepts it at all.

Nothing here describes a particular person. Questions about a diagnosis, a report or a family history belong with the treating neurologist and a genetic counsellor.

Sources for this page