A subtype of sporadic prion disease mimicking fatal familial insomnia

Objective: To establish a variant of sporadic prion disease as the sporadic form of fatal familial insomnia (FFI). Background: FFI is a recently descr ibed prion disease characterized clinically by severe sleep impairment, dys autonomia, and motor signs, and pathologically by atrophy of thalamic nucle i, especially the medial dorsal and anterior ventral, and of the inferior o live. FFI is linked to the D178N mutation coupled with the methionine codon at position 129 in the prion protein gene (PRNP). It is also identified by the properties of the abnormal prion protein (PrPSc), which has the relati ve molecular mass of 19 kDa, corresponding to the so-called type 2, and a m arked underrepresentation of the unglycosylated form relative to the diglyc osylated and monoglycosylated forms. Methods: Clinical, pathologic, PrPSc, and PRNP data from 5 subjects with a sporadic prion disease phenotypically similar to FFI were collected and analyzed. Results: All 5 subjects had a d isease clinically similar and histopathologically virtually identical to FF I. PrPSc type 2 was present in all subjects in amount and distribution simi lar to those of FFI. However, the PrPSc did not show the striking underrepr esentation of the unglycosylated isoform of the protein that is characteris tic of FFI. Moreover, none of the subjects had the D178N PRNP mutation but all were homozygous for methionine at codon 129. Conclusion: This condition is likely to represent the sporadic form of FFI and the term "sporadic fat al insomnia" is proposed.