'PrP systemic deposition disease': clinical and pathological characteristics of novel familial prion disease with 2-bp deletion in codon 178

Background and purpose A novel TYPE of prion disease associated mainly with autonomic‐sensory polyneuropathy was reported by us previously. Methods Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control). Results Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2‐bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon. Conclusion The present unique 2‐bp deletion (CT) in codon 178 induced a ‘PrP systemic deposition disease’ such as pan‐autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology.