Merck Manual

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Prion Disease Associated With Diarrhea and Autonomic Neuropathy

(Prion Protein Systemic Amyloidosis)


Brian Appleby

, MD, Case Western Reserve University

Reviewed/Revised Nov 2022

Prion disease associated with diarrhea and autonomic neuropathy describes an inherited prion disease that manifests with peripheral rather than central nervous system symptoms.

Prion disease associated with diarrhea and autonomic neuropathy was identified in 2013 in an extended British family. A similar disease has been reported in an Italian family.

This disease differs from other prion diseases because

  • Prion amyloid is not limited to the central nervous system (CNS) but is distributed in peripheral nerves and internal organs; thus, peripheral symptoms predominate initially, and CNS symptoms occur late.

  • It is associated with a novel mutation in the prion gene (Y163X mutation; Y162X mutation in the Italian family) that results in truncation of the mutated prion protein; thus, the mutated proteins lacks the anchor that typically tethers the prion protein to cell membranes, presumably favoring the prion protein's floating in body fluids and migrating to other tissues.

This new prion disease shows that a novel mutation can radically change where the abnormal proteins deposit and which symptoms they cause, and it suggests that the diagnosis of prion disease should be considered in patients with unexplained chronic diarrhea and neuropathy or with an unexplained syndrome similar to familial amyloid polyneuropathy (which causes autonomic and peripheral neuropathy).

Symptoms begin in early adulthood; they include chronic watery diarrhea, autonomic failure (eg, urinary retention, urinary incontinence, orthostatic hypotension), and a primarily sensory peripheral polyneuropathy. Cognitive decline and seizures occur when patients are in their 40s or 50s.

The disease progresses over decades; patients may live up to 30 years after symptoms develop.

There is only symptomatic treatment for this disorder.

NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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