A Patient Homozygous for the E200K Mutation from a Family of the Slovak Cluster of Genetic Creutzfeldt-Jakob Disease

The first report of a patient homozygous for the E200K mutation of the prion protein gene in the Slovak cluster of 227 genetic Creutzfeldt-Jakob disease cases is presented. Consanguinity between parents or in the family was not reported. Clinical course, epidemiological data, family history, results obtained by immunoblotting, histopathology and immunohistochemistry are described and compared with patients heterozygous for the same mutation. While no striking difference was observed in neurological and psychiatric symptomatology or duration of symptomatic course, a significant age difference was found. The patient homozygous for the E200K mutation is the youngest case (29 years old) of Creutzfeldt-Jakob disease in Slovakia. The significant difference in age at the time of death between the patient and his affected relative from the previous generation (25 years) is in agreement with the concept of anticipation that characterizes familial cases of the Creutzfeldt-Jakob disease in Slovakia. This emphasises the decreasing age of onset of the disease in carriers of the E200K mutation in successive generations. This is important with respect to early diagnosis of the disease and prevention of iatrogenic transmission. Unexpected survival of E200K carriers aged 90 years or over without any signs of Creutzfeldt-Jakob disease, provides 1. further evidence of the incomplete penetrance of the Central European type of the E200K mutation and 2. emphasises the possible role of co-factors and triggering stimuli. Their more detailed study and elucidation may contribute to prevention of clinical manifestation of the genetic Creutzfeldt-Jakob disease in asymptomatic carriers of the most frequent, worldwide spread E200K mutation.