Case 38 - Young man with slow cognitive decline

Summary

This chapter describes the slow cognitive decline using the case of a 31-year-old right-handed man (patient FA) who was referred for clinical evaluation due to a 3-year history of progressive deterioration of memory and academic performance as an example. Prion-related syndrome was part of the differential diagnosis. FA had a typical clinical presentation suggestive of Gerstmann-Straussler-Scheinker syndrome (GSSS), but the diagnosis could not be confirmed (absence of PRPN mutations). One-third of carriers of PRNP mutations have negative family history. P102L is a missense mutation that substitutes a lysine for a proline at codon 102. Although homozygosis for methionine at codon 129, like observed in the patient FA, confers vulnerability to prion diseases, the molecular pathology of this case remains unknown since PRPN genotype did not reveal a known PRPN GSSS mutation. Brain necropsy in the patient revealed typical GSSS neuropathological features, with amyloid plaques immunoreactive for PrP displaying multicentric morphology.