Novel Prion Disease With Peripheral Symptoms Identified

November 20, 2013

Researchers from the United Kingdom have identified a new clinical syndrome caused by a novel genetic prion disease that causes severe diarrhea and peripheral neuropathies.

They believe this discovery may also help improve understanding of the basis for other neurodegenerative conditions, such as Alzheimer's disease and Parkinson's disease.

The researchers, led by Simon Mead, MD, University College London, report their findings in the November 14 issue of the New England Journal of Medicine.

Dr. Mead explained to Medscape Medical News that this syndrome is the first prion disease presenting with peripheral symptoms ever discovered.

"That we identified it as a prion disease was a great surprise as prion disease normally causes dementia and has a very fast-running course, from presentation to death in just a few months. This condition, however, is not characterized by dementia but instead more by neuropathies causing severe diarrhea and other peripheral symptoms, and has a slow course, with the patients living with the condition for up to 30 years.

"There may be other neurologists or gastrointestinal specialists who have patients with these symptoms and haven't been able to diagnose the problem," he added. "If so, they should think about the possibility of this novel prion disease."

Prion Protein Systemic Amyloidosis

The syndrome is as yet unnamed, but the research team is considering the term "prion protein systemic amyloidosis."

Dr. Mead explained that the affected family presented with 11 members showing symptoms of this syndrome, with severe diarrhea; neuropathy, manifesting as loss of feelings in feet; and loss of bladder control and postural hypotension. The researchers studied 6 of the affected family members in detail, along with autopsy or biopsy samples obtained from 5 of them, and found abnormal prion protein deposits.

Prions are infectious protein particles but, unlike bacteria or viruses, are not living things themselves. However, they can be transmitted by chemical reactions, or they can occur naturally and be inherited, as in this family. They cause the normal prion protein to change shape or become unstable. Prion diseases have so far been confined to the brain, but in this condition, the abnormal prion proteins were found all over the body.

The researchers then sequenced the prion gene and identified a truncation mutation, which caused the protein to be only half-formed. Dr. Mead explained: "This causes the part of the protein that attaches to cells to be missing so it floats around in body fluids, and that's how it gets into other tissues and organs, which is why we're seeing peripheral symptoms."

… no one would ever have thought that prion disease would cause diarrhea. This has never been seen before to our knowledge. Dr. Simon Mead

"This family was so hard to diagnose — no one would ever have thought that prion disease would cause diarrhea. This has never been seen before to our knowledge," Dr. Mead commented. Although there is no cure at present, the researchers are developing an antibody that could become a treatment.

On a broader level, the authors believe that protein misfolding, as has occurred here, is the basis for most neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease.

"A single mutation causing a protein to misfold can radically change where they deposit and how toxic they are," Dr. Mead noted. "This could explain why individual neurodegenerative diseases have such heterogeneity — different symptoms and time courses — because the protein is deposited in different parts of the brain."

He added: "Our novel prion disease is a stunning example of a misfolding disease. Through extreme examples such as this, it may be possible to shed more light on other neurodegenerative diseases, such as Alzheimer's and Parkinson's. For example in Alzheimer's, there may be a mutation in the amyloid precursor protein so that it deposits in different tissues."

The study was supported by grants from the UK Medical Research Council, the Reta Lila Weston Institute of Neurological Studies, Alzheimer's Research UK, the Multiple System Atrophy Trust, the National Institute for Health Research (NIHR) Biomedical Research Center at the University College London Hospitals NHS Foundation Trust and University College London, the NIHR Dementia Biomedical Research Unit, the National Institutes of Neurological Diseases and Stroke, and Office of Rare Diseases Research; a Welcome Trust Senior Clinical Fellowship; and a Wellcome Trust/MRC Neurodegeneration award. Disclosures for the researchers are available at

N Engl J Med. 2013;369:1904-1914. Abstract


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.