title: Distinct pathological phenotypes of Creutzfeldt-Jakob disease in recipients of prion-contaminated growth hormone.
abstract: BACKGROUND
  The present study compares the clinical, pathological and molecular features of a United States (US) case of growth hormone (GH)-associated Creutzfeldt-Jakob disease (GH-CJD) (index case) to those of two earlier referred US cases of GH-CJD and one case of dura mater (d)-associated CJD (dCJD). All iatrogenic CJD (iCJD) subjects were methionine (M) homozygous at codon 129 (129MM) of the prion protein (PrP) gene and had scrapie prion protein (PrP(Sc)) type 1 (iCJDMM1).
  
  
  RESULTS
  The index subject presented with ataxia, weight loss and changes in the sleep pattern about 38 years after the midpoint of GH treatment. Autopsy examination revealed a neuropathological phenotype reminiscent of both sCJDMV2-K (a sporadic CJD subtype in subjects methionine/valine heterozygous at codon 129 with PrP(Sc) type 2 and the presence of kuru plaques) and variant CJD (vCJD). The two earlier cases of GH-CJDMM1 and the one of dCJDMM1 were associated with neuropathological phenotypes that differed from that of the index case mainly because they lacked PrP plaques. The phenotype of the earlier GH-CJDMM1 cases shared several, but not all, characteristics with sCJDMM1, whereas dCJDMM1 was phenotypically indistinguishable from sCJDMM1. Two distinct groups of dCJDMM1 have also been described in Japan based on clinical features, the presence or absence of PrP plaques and distinct PK-resistant PrP(Sc) (resPrP(Sc)) electrophoretic mobilities. The resPrP(Sc) electrophoretic mobility was, however, identical in our GH-CJDMM1 and dCJDMM1 cases, and matched that of sCJDMM1.
  
  
  CONCLUSIONS
  Our study shows that receipt of prion-contaminated GH can lead to a prion disease with molecular features (129MM and PrP(Sc) type 2) and phenotypic characteristics that differ from those of sporadic prion disease (sCJDMM1), a difference that may reflect adaptation of "heterologous" prion strains to the 129MM background.
authors.affiliation: Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, USA. ixc20@case.edu.|Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy. ixc20@case.edu.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cali
authors.affiliation: Department of Neurology, Kaiser Permanente Sunnyside Medical Center, Clackamas, OR, USA.
authors.forename: Cathleen J
authors.initials: CJ
authors.lastname: Miller
authors.affiliation: Departments of Laboratory Medicine & Pathology and Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Parisi
authors.affiliation: Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Geschwind
authors.affiliation: Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
authors.affiliation: Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schonberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000473:pathology*; D016643:Encephalopathy, Bovine Spongiform / Q000145:classification / Q000473:pathology*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D010641:Phenotype; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D018620:PrPSc Proteins; D013006:Growth Hormone