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Updated: Jul 2, 2025
Protein Misfolding Cyclic Amplification of Prions
Published on: November 7, 2012
Variably protease-sensitive prionopathy with methionine homozygosity at codon 129 in the prion protein gene
Frederikke Kragh Clemmensen1, Ausrine Areskeviciute2, Eva Løbner Lund2
1Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark frederikke.kragh.clemmensen@regionh.dk.
Abstract:
Variably protease-sensitive prionopathy (VPSPr) is a recently characterised rare subtype of sporadic prion disease, mainly affecting individuals with valine homozygosity at codon 129 in the prion protein gene, with only seven methionine homozygote cases reported to date. This case presents clinical, neuropathological and biochemical features of the eighth VPSPr case worldwide with methionine homozygosity at codon 129 and compares the features with the formerly presented cases.The patient, a woman in her 70s, presented with cognitive decline, impaired balance and frequent falls. Medical history and clinical presentation were suggestive of a rapidly progressive dementia disorder. MRI showed bilateral thalamic hyperintensity. Cerebrospinal fluid real-time quaking-induced conversion was negative, and the electroencephalogram was unremarkable. The diagnosis was established through post-mortem pathological examinations. VPSPr should be suspected in rapidly progressive dementia lacking typical features or paraclinical results of protein misfolding diseases.
Insights
Variably protease-sensitive prionopathy (VPSPr) is a rare prion disease. This report details the eighth methionine-homozygous case, highlighting unique clinical and pathological features.
Area of Science:
- Neurology
- Neuroscience
- Pathology
Background:
- Variably protease-sensitive prionopathy (VPSPr) is a rare subtype of sporadic prion disease.
- It predominantly affects individuals homozygous for valine at codon 129 of the prion protein gene.
- Methionine homozygosity at codon 129 is exceptionally rare in VPSPr.
Observation:
- This case study describes an eighth VPSPr patient with methionine homozygosity at codon 129.
- The patient, a woman in her 70s, exhibited rapid cognitive decline, impaired balance, and falls.
- Clinical presentation suggested a rapidly progressive dementia; MRI revealed bilateral thalamic hyperintensity.
Findings:
- Cerebrospinal fluid real-time quaking-induced conversion (RT-QuIC) was negative.
- Electroencephalogram (EEG) findings were unremarkable.
- Post-mortem pathological examinations confirmed the diagnosis of VPSPr.
Implications:
- VPSPr diagnosis should be considered in rapidly progressive dementia cases lacking typical features or diagnostic biomarkers.
- This case expands the understanding of VPSPr's genetic associations and clinical spectrum.
- Further research is needed to elucidate the pathogenesis and diagnostic criteria for VPSPr in methionine homozygotes.
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