We discuss a case of a 58 yo previously healthy man from rural China who presented with initial symptoms of restlessness, insomnia, and depression that progressed to diffuse weakness, gait ataxia, and worsening encephalopathy. He underwent extensive workup, including MRI brain, body PET, multiple lumbar punctures, and EEG, all of which were unremarkable. Serum inflammatory, infectious, and paraneoplastic panels were unrevealing. He had hypoxia with respiratory failure, requiring tracheostomy. Physical exam continued to be notable for encephalopathy to the point of not being able to follow commands, extreme cachexia that included significant temporal wasting, and diffuse weakness causing him to be bedbound. He was treated empirically for seronegative autoimmune encephalitis, which included intravenous immunoglobulin, steroids, and 4 sessions of plasma exchange, with minimal improvement in mental status. 

Family history, provided by his wife, was significant for an unknown, possibly neurologic disorder that also affected patient’s father and sister in their 50s and early 60s. Out of concern for a possible genetic cause, whole exome sequencing was performed that identified a pathogenic variant in PRNP gene. He was specifically found to have the D178N0129M haplotype, which is typically seen in FFI. Genetic counseling was offered to his 7 remaining siblings.