title: Human prion diseases in the Netherlands (1998-2009): clinical, genetic and molecular aspects.
abstract: Prion diseases are rare and fatal neurodegenerative disorders that can be sporadic, inherited or acquired by infection. Based on a national surveillance program in the Netherlands we describe here the clinical, neuropathological, genetic and molecular characteristics of 162 patients with neuropathologically confirmed prion disease over a 12-year period (1998-2009). Since 1998, there has been a relatively stable mortality of Creutzfeldt-Jakob disease (CJD) in the Netherlands, ranging from 0.63 to 1.53 per million inhabitants per annum. Genetic analysis of the codon 129 methionine/valine (M/V) polymorphism in all patients with sporadic CJD (sCJD) showed a trend for under-representation of VV cases (7.0%), compared with sCJD cohorts in other Western countries, whereas the MV genotype was relatively over-represented (22,4%). Combined PrP(Sc) and histopathological typing identified all sCJD subtypes known to date, except for the VV1 subtype. In particular, a "pure" phenotype was demonstrated in 60.1% of patients, whereas a mixed phenotype was detected in 39.9% of all sCJD cases. The relative excess of MV cases was largely accounted for by a relatively high incidence of the MV 2K subtype. Genetic analysis of the prion protein gene (PRNP) was performed in 161 patients and showed a mutation in 9 of them (5.6%), including one FFI and four GSS cases. Iatrogenic CJD was a rare phenomenon (3.1%), mainly associated with dura mater grafts. Three patients were diagnosed with new variant CJD (1.9%) and one with variably protease-sensitive prionopathy (VPSPr). Post-mortem examination revealed an alternative diagnosis in 156 patients, most commonly Alzheimer's disease (21.2%) or vascular causes of dementia (19.9%). The mortality rates of sCJD in the Netherlands are similar to those in other European countries, whereas iatrogenic and genetic cases are relatively rare. The unusual incidence of the VV2 sCJD subtype compared to that reported to date in other Western countries deserves further investigation.
authors.affiliation: Dutch Surveillance Centre for Prion Diseases, University Medical Centre Utrecht, Utrecht, The Netherlands. c.jansen@umcutrecht.nl
authors.forename: Casper
authors.initials: C
authors.lastname: Jansen
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.forename: Carla A
authors.initials: CA
authors.lastname: Ibrahim-Verbaas
authors.forename: Maaike
authors.initials: M
authors.lastname: Schuur
authors.forename: Rosaria
authors.initials: R
authors.lastname: Strammiello
authors.forename: Patrizia
authors.initials: P
authors.lastname: Corrado
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Bishop
authors.forename: Willem A
authors.initials: WA
authors.lastname: van Gool
authors.forename: Marcel M
authors.initials: MM
authors.lastname: Verbeek
authors.forename: Frank
authors.initials: F
authors.lastname: Baas
authors.forename: Wesley
authors.initials: W
authors.lastname: van Saane
authors.forename: Wim G M
authors.initials: WG
authors.lastname: Spliet
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Jansen
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D007562:Creutzfeldt-Jakob Syndrome / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D017096:Prion Diseases / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D011328:Prions / Q000378:metabolism
chemical_list: D011328:Prions