Mead S, Ghandi S, Beck J, et.al.;
N Engl J Med. 2013 Nov 14;369 (20):1904-14
Submitted by Carlos A. Luciano, MD
About the Study
Prion diseases are transmissible, sporadic, or inherited diseases usually associated with progressive dementia or ataxia and not with dysautonomia or peripheral neuropathy. In a study from the Medical Research Council Prion Unit at University College, London, Drs. Mead, Collinge, and colleagues described a novel and distinct phenotype of a prion disease in a British kindred where patients presented in their 30s with diarrhea followed by symptoms and signs of a mixed predominantly sensory and autonomic polyneuropathy. Sequencing of the gene encoding prion protein (PRNP) revealed a novel PRNP Y163X truncation mutation. The disease was inherited in a dominant fashion and had an unusually prolonged course later associated with cognitive decline and seizures. In addition, the deposition of prion protein was seen in peripheral organs including bowel and peripheral nerve, which is unusual for prion diseases.
This is the first description of a unique and novel phenotype for a prion disease, with involvement of the gastrointestinal and peripheral nervous system with prominent autonomic dysfunction, evidence of widespread prion protein deposition in tissues other than the brain, and an unusually prolonged clinical course. Linked to a novel truncated mutation of the Prion Protein Gene (PRNRP), this novel phenotype supports the possibility of differences in expression based on differences in the alteration of the protein. Clinicians should consider the possibility of this novel inherited prion disease in patients that may appear to have a clinical picture suggestive of a familial mixed sensory and autonomic neuropathy, similar to inherited amyloid neuropathy.
About the News Science Editorial Board
The board helps to highlight significant, timely science news items for AANEM members. It reviews articles in journals and websites, identifies newsworthy items in the field each month, and writes article summaries.
Zaeem Siddiqi, MD, PhD (chair); Shan (Sarah) Chen, MD, PhD; Brent Goodman, MD; Ileana Howard, MD; Nicholas Johnson, MD; Carlos Luciano, MD; Andrew Tarulli, MD; Leigh Maria Ramos-Platt, MD