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Cases of iatrogenic CJD still occur in the UK 30 years after administration of human pituitary-derived growth hormone ceased. Rudge et al. report a change over time in genotype profile at polymorphic codon 129 of the human prion protein gene in UK patients, distinct from that seen in other countries.

Human-to-human transmission of Creutzfeldt–Jakob disease (CJD) has occurred through medical procedures resulting in iatrogenic CJD (iCJD). One of the commonest causes of iCJD was the use of human pituitary-derived growth hormone (hGH) to treat primary or secondary growth hormone deficiency. As part of a comprehensive tissue-based analysis of the largest cohort yet collected (35 cases) of UK hGH-iCJD cases, we describe the clinicopathological phenotype of hGH-iCJD in the UK. In the 33/35 hGH-iCJD cases with sufficient paraffin-embedded tissue for full pathological examination, we report the accumulation of the amyloid beta (Aβ) protein associated with Alzheimer’s disease (AD) in the brains and cerebral blood vessels in 18/33 hGH-iCJD patients and for the first time in 5/12 hGH recipients who died from causes other than CJD. Aβ accumulation was markedly less prevalent in age-matched patients who died from sporadic CJD and variant CJD. These results are consistent with the hypothesis that Aβ, which can accumulate in the pituitary gland, was present in the inoculated hGH preparations and had a seeding effect in the brains of around 50% of all hGH recipients, producing an AD-like neuropathology and cerebral amyloid angiopathy (CAA), regardless of whether CJD neuropathology had occurred. These findings indicate that Aβ seeding can occur independently and in the absence of the abnormal prion protein in the human brain. Our findings provide further evidence for the prion-like seeding properties of Aβ and give insights into the possibility of iatrogenic transmission of AD and CAA.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-017-1703-0) contains supplementary material, which is available to authorized users.

Size-exclusion chromatography, used in non-Wilhelmi preparation methods, may prevent CJD infection. Susceptibility to CJD may vary with age, and susceptibility may be present in only a few percent of the population.

SUMMARY Longitudinal height data and physical development were assessed in 29 boys and 12 girls taking long term steroid treatment for steroid sensitive nephrotic syndrome. Growth in both boys and girls, assessed by changes in height standard deviation score (AHt SDS), worsened significantly with chronological age. There was a significant negative correlation between AHt SDS and duration of treatment in boys, but not in girls. There was no correlation between AHt SDS and relapse rate or the use of cyclophosphamide. In the boys, Ht SDS decreased significantly only after the age of 10 years and was associated with delay in the appearance of secondary sexual characteristics.Eight adolescent boys were assessed endocrinologically by an overnight hormone profile. Blunting of the pulsatility of growth hormone and gonadotrophins was seen in six. Normal profiles were seen in two subjects who were both off steroid treatment at the time of study.Abnormal endocrine function in adolescent boys treated long term for steroid sensitive nephrotic syndrome corresponded with the clinical picture of delayed onset of puberty, which accounted for severe growth retardation in a substantial proportion of subjects.