Background: PraderWilli syndrome (PWS) is characterized by a switch in early childhood from failure to thrive to excessive weight gain and hyperphagia with impaired satiety. The underlying mechanism for this switch may involve hyperghrelinemia, but only poor data exists regarding levels of acylated ghrelin (AG), unacylated ghrelin (UAG), and the AG/UAG ratio in PWS.
Objective and hypotheses: To investigate plasma levels of AG and UAG in PWS, compared with the levels of obese and lean controls. To investigate associations in PWS between AG and UAG levels, and BMI and eating behaviour.
Method: The AG and UAG levels of 138 children and young adults with PWS (range 0.229.4 years) are compared with age-matched obese (50) and lean (39) controls. AEBSF, inhibitor of des-acylation of AG, was added to the blood samples.
Results: AG levels were significantly higher in PWS than in lean controls. UAG levels in PWS were similar to lean controls, which resulted in a significantly raised AG/UAG ratio. Obese controls had lowest AG and UAG levels compared with PWS and lean controls. UAG is more decreased than AG in obese controls, which resulted in the highest AG/UAG ratio of the three groups. We found no difference in gender or genetic subtype of PWS. In PWS, age and BMI SDS were strongly correlated with nutritional phases according to Miller (both P<0.000001). In these patients, AG, UAG levels, and AG/UAG ratio were inversely associated with the nutritional phase (P=0.004, P<0.00001 and P=0.015, respectively). Raised BMI was associated with lower UAG levels, even after adjustment for age and gender (P=0.008).
Conclusion: Our findings provide a rationale for a role of an abnormal AG/UAG ratio in eating behavior in PWS.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology