Prospective 10-year surveillance of human prion diseases in Japan

Abstract

We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over the past 10 years, since 1999. We obtained information on 1685 Japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n=180, 14.7%) and probable (n=1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt-Jakob disease which also included possible cases (n=13, 1.1%). They were classified into 922 (75.5%) with sporadic Creutzfeldt-Jakob disease, 216 (17.7%) with genetic prion diseases, 81 (6.6%) with acquired prion diseases, including 80 cases of dura mater graft-associated Creutzfeldt-Jakob disease and one case of variant Creutzfeldt-Jakob disease, and three cases of unclassified Creutzfeldt-Jakob disease (0.2%). The annual incidence rate of prion disease ranged from 0.65 in 1999 to 1.10 in 2006, with an average of 0.85, similar to European countries. Although methionine homozygosity at codon 129 polymorphism of the prion protein gene was reported to be very common (93%) in the general Japanese population, sporadic Creutzfeldt-Jakob disease in Japan was significantly associated with codon 129 homozygosity (97.5%), as reported in western countries. In sporadic Creutzfeldt-Jakob disease, MM1 type (Parchi's classification) is the most common, as in western countries. Among atypical sporadic Creutzfeldt-Jakob disease cases, the MM2 type appeared most common, probably related to the very high proportion of methionine allele in the Japanese population. As for iatrogenic Creutzfeldt-Jakob disease, only dura mater graft-associated Creutzfeldt-Jakob disease cases were reported in Japan and, combined with the data from previous surveillance systems, the total number of dura mater graft-associated Creutzfeldt-Jakob disease was 138, comprising the majority of worldwide dura mater graft-associated Creutzfeldt-Jakob disease patients. Regarding genetic prion diseases, the most common mutation of prion protein gene was V180I (41.2%), followed by P102L (18.1%), E200K (17.1%) and M232R (15.3%), and this distribution was quite different from that in Europe. In particular, V180I and M232R were quite rare mutations worldwide. Patients with V180I or M232R mutations rarely had a family history of prion diseases, indicating that a genetic test for sporadic cases is necessary to distinguish these from sporadic Creutzfeldt-Jakob disease. In conclusion, our prospective 10-year surveillance revealed a frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease, and unique phenotypes of sporadic Creutzfeldt-Jakob disease and genetic prion diseases related to the characteristic distribution of prion protein gene mutations and polymorphisms in Japan, compared with those in western countries.

Scientific Opinion on a request for a review of a scientific publication concerning the zoonotic potential of ovine scrapie prions

“…Despite these considerations, mortality rates are remarkably similar in the majority of countries in Europe (Kovacs et al, 2007;Gubbels et al, 2012;Jansen et al, 2012;Brandel et al, 2013) and are consistent with recent national surveillance data from Argentina (Begue et al, 2011), Australia (Klug et al, 2013b) and Japan (Nozaki et al, 2010). It is of note that Australia has never reported a case of Classical scrapie.…”

Creutzfeldt-Jakob disease associated with a V203I homozygous mutation in the prion protein gene

“…Although no histopathological examinations were performed, the clinical course to akinetic mutism, findings of the brain MRI and EEG, and elevation of tau and 14-3-3 proteins in the CSF were consistent with those typical of CJD patients. 3 The genotype frequency of the V203I mutation in the genetic prion diseases has been reported as 0.9% in the Japanese (2/216 cases) 4 and 1.2% in Europeans (5/425 cases). 5 There have been 3 case reports of fCJD associated with the V203I heterozygous mutation so far;…”

Serum tau protein as a marker for the diagnosis of Creutzfeldt-Jakob disease

“…Probably due to very high proportion of MM genotype at PrP codon 129 in the Japanese population (93%) [22], all the 12 patients with sporadic CJD in this study had MM genotype at codon 129, including 3 with the MM2-cortical form; the MM2-type sporadic CJD is common among atypical CJD cases in Japan [22]. While, no patients with VV or MV genotype, rare genotypes in Japan [22], could be included in this study, although VV2-type sporadic CJD is the second commonest form in European countries and the USA [11] [23]. In addition, to reveal the statistical significance in serum-tau levels for the MM2-cortical form of sporadic CJD, further study with a larger number of the patients is necessary.…”