In this chapter, we summarize the clinical, neuropathologic, biochemical, and diagnostic features of dura mater graft- and human pituitary-derived growth hormone-associated CJD patients for the appropriate diagnosis of iatrogenic CJD.
The identification of Creutzfeldt-Jacob disease in individuals who received pituitary-derived GH led to heightened surveillance for safety issues related to recombinant human GH (rhGH).
Based on extensive modelling of human prion transmission barriers in transgenic mice expressing human prion protein on a mouse prion protein null background, the temporal distribution of codon 129 genotypes within the cohort of patients with iatrogenic Creutzfeldt-Jakob disease in the UK suggests that there was a point source of infecting prion contamination of growth hormone derived from a patient with Creutzfeldt-Jakob disease expressing prion protein valine 129.
More than two hundred individuals developed Creutzfeldt-Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions.
Epidemiological studies on human transmissible spongiform encephalopathies (Creutzfeldt-Jakob Disease, CJD) have shown that the agent could be transmitted by highly infectious tissues like brain, spinal cord or retina and medicinal products derived from these tissues (i.e. human growth hormone, dura mater).
Since homozygosity MM at codon 129 of the prion protein gene is a recognised risk factor in all forms of Creutzfeldt-Jakob disease (CJD), we studied the distribution of codon 129 polymorphism in patients in France and in the UK with CJD transmitted iatrogenically by human growth hormone.
The proportion of recipients acquiring CJD from growth hormone varies from 0.3 to 4.4% in different countries, and acquisition from dura mater varies between 0.02 and 0.05% in Japan (where most cases occurred).
The most frequent of the latter include acquired forms secondary to injections of human cadaveric pituitary-derived growth hormone and the new variant of CJD--probably related to bovine spongiform encephalopathy.
We tested DNA from 15 centrally infected cases of iatrogenic Creutzfeldt-Jakob disease (CJD) (dura mater or corneal homografts and stereotactic EEG electrodes), 11 peripherally infected cases (native human growth hormone or gonadotrophin), and 110 control individuals for the presence of mutations in the chromosome 20 amyloid gene.
The spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) has been transmitted to man via administration of growth hormone and gonadotropin extracted from large pooled batches of human cadaveric pituitary glands.