Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: Changes during development

Background: Prader-Willi syndrome (PWS) is associated with failure to thrive in infancy and progressive hyperphagia and obesity in childhood. This progressive weight gain is associated with hyperghrelinaemia and increased insulin sensitivity. The role of ghrelin excess in the pathogenesis of obesity is unclear. Objective: To determine if high ghrelin levels precede the onset of obesity in young PWS children. Design and methods: A cross-sectional study of 33 infants with PWS and 28 healthy control subjects (C). Fasting ghrelin and other satiety hormones were measured. Results: Median total serum ghrelin in young children with PWS trended higher, but did not differ significantly from those in C of similar age, weight-for-age z-score and sex. However, there was more variability in ghrelin concentrations of young PWS. Eleven of 33 PWS subjects had ghrelin levels greater than the 95th percentile for ghrelin values in the C subjects (> 2871 pg/ml). Six of the PWS subjects with high ghrelin levels had weight-for-age z-scores < 0. Ghrelin concentrations in PWS and C infants exceeded those in older children. In youngsters with PWS, leptin was higher, suggesting a relative excess of fat to lean body mass and plasma adiponectin was increased. Conclusions: Young infants with PWS who have not yet developed hyperphagia or obesity have median fasting ghrelin levels similar to controls. However, a subset (33%) of young PWS is hyperghrelinaemic; approximately one-half of those with hyperghrelinaemia have BMI z-score < 0. The age-related decline in ghrelin is blunted in PWS.