Fatal insomnia in a case of familial Creutzfeldt-Jakob disease with the codon 200^Lys mutation

Lugaresi et al ^[1] reported a familial syndrome involving insomnia and dysautonomia with selective degeneration of the thalamic nuclei. The autosomal dominant mode of inheritance and additional clinical features, such as myoclonus, ataxia, and spongiform changes, in one family member led Medori et al. to establish that fatal familial insomnia (FFI) is a prion disease linked to a codon 178 aspargine-to-aspartic acid mutation in the PRNP gene. ^[2] This finding was of special interest because this particular mutation was linked to familial Creutzfeldt-Jakob disease (CJD) in a number of European kindreds. ^[3-6] FFI is distinguishable from CJD by the presence of insomnia and predominant thalamic involvement, and the fact that both seemed to result from a common genotype was surprising. This was resolved by the discovery that a common polymorphism at PRNP codon 129 determines the phenotypic expression of the 178^Asn mutation: The 129^Met-178Asn allele segregates with FFI and the 129^Val-178Asn allele segregates with familial CJD. ^[7]

The large cluster of familial CJD in Israel is linked to a PRNP 200^Lys mutation. ^[8,9] We report a patient with severe insomnia, including a complete histopathologic autopsy examination of the brain and molecular analysis of the PRNP gene. This patient is case number 13 of a recent report about the phenotypic heterogeneity in familial CJD linked to the 200^Lys mutation. ^[10]

Case report.

A 64-year-old unmarried woman presented with insomnia and confusion. She had been healthy up to 2 months earlier, when the family noticed minor changes in her personality insofar as she responded unusually strongly to criticism. She continued to live alone unaided until 2 weeks before being examined. Her sister then noticed she was confused and took her in to her own house. During the next 2 weeks, the patient could not sleep and would …