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Prader-Willi syndrome (PWS), first described in 1956, is considered as a paradigm of a neurodevelopmental disorder with severe and early obesity with hyperphagia and impaired satiety. The improved knowledge in the natural history and recent data on genetics offer new perspectives for understanding the metabolic and endocrine dysfunctions and possibly for treatment. Natural history of the disease has been described due to the early diagnosis performed in the first months of life and various nutritional phases have been described. In addition, there is clear evidence that the abnormal feeding behavior is included in the behavioral problems. Brain imaging studies have shown that some brain regions may be important in PWS. The role of SNORD116 gene cluster is detailed and its links with circadian rhythm and brain and hypothalamus development. Pathophysiology of the abnormal ghrelin levels and of OT dysfunction is documented. While no effect on appetite and weight regulation has been reported with ghrelin antagonists, OT has been shown to improve some of the behavioral problems in adults. We discuss our hypothesis of an abnormal ghrelin/OT/dopamine pathway which may explain the switch of nutritional phases and behavior. These new aspects offer an opportunity for therapeutic use and possible early intervention., (© 2014 S. Karger AG, Basel.)

Background: High plasma ghrelin levels have been reported in Prader-Willi syndrome (PWS). However, little is known about plasma ghrelin in these children during the first years of life characterized by a failure to thrive., Objective: The objective of the study was to investigate total plasma ghrelin levels in children with PWS and controls from 2 months to 17 years., Subjects and Methods: Forty children with PWS [24 boys, 16 girls, median age 3.6 yr, median body mass index (BMI) Z-score 0.3] were compared with 84 controls (57 boys, 27 girls, median age 4.2 yr median BMI Z-score 0.1). Children were then divided into two groups according to age and GH treatment., Results: Median plasma ghrelin levels were significantly higher in children with PWS, compared with controls at any age (568 vs. 173, P < 0.0001) and decreased with age in both groups (P < 0.0001). In the whole group of PWS, we found an inverse relationship between ghrelin and BMI Z-score, insulin, homeostasis model assessment insulin resistance index, leptin, and lean mass. Plasma ghrelin levels were higher in children with PWS than controls, both in the youngest children below 3 yr who were not receiving GH (771 vs. 233, P < 0.0001) and in the children older than 3 yr, all of whom were treated with GH (428 vs. 159, P < 0.0001)., Conclusions: Plasma ghrelin levels in children with PWS are elevated at any age, including during the first years of life, thus preceding the development of obesity.

Background: Adolescents with idiopathic scoliosis display high ghrelin levels. As hyperghrelinemia is found in patients with PWS and early-onset scoliosis (EOS) is highly prevalent in these patients, our aims were to explore (1) whether ghrelin levels differ between those with and without EOS and correlate with scoliosis severity, and (2) whether ghrelin levels in the first year of life are associated with the later development of EOS.Methods: We used a case control study design for the first question and a longitudinal design for the second. Patients with PWS having plasma ghrelin measurements recorded between 2013 and 2018 in our database were selected and 30 children < 10 years old with EOS and 30 age- and BMI-matched controls without EOS were included. The Cobb angle at diagnosis was recorded. In addition, 37 infants with a ghrelin measurement in the first year of life were followed until 4 years of age and assessed for EOS. Total ghrelin (TG), acylated (AG) and unacylated ghrelin (UAG), and the AG/UAG ratio were analyzed.Results: EOS children had an AG/UAG ratio statistically significantly lower than controls. The Cobb angle was positively correlated with TG and UAG. TG and AG in the first year of life were higher in infants who later develop EOS without reaching a statistically significant difference.Conclusions: Our results suggest that ghrelin may play a role in the pathophysiology of EOS in PWS. Higher ghrelinemia in the first year of life required careful follow-up for EOS. [ABSTRACT FROM AUTHOR]

Background: A control study was designed to investigate circulating Ghrelin levels in adolescent girls with adolescent idiopathic scoliosis (AIS) and controls. Eating behavioral disorders, endocrine disorders, abnormal growth pattern and osteopenia have been well documented in AIS. Ghrelin is an orexigenic hormone produced by the stomach which reflects body weight changes and stimulates growth hormone secretion. Recently, it has been shown to be associated with bone metabolism and eating behavior. However, the circulating levels of ghrelin have never been evaluated in AIS patients. Methods: Forty nine AIS girls and 15 controls were included. Anthropometric parameters and fasting circulating total ghrelin were measured. Curve severity was evaluated in AIS girls. The relationships between ghrelin and age, body weight, height, body mass index (BMI), BMI Z-score and corrected anthropometric parameters were analyzed in AIS girls and controls. Results: There was no significant difference in body weight, height, BMI or BMI Z-score between AIS and controls. Serum ghrelin level was 1.8 fold higher in AIS girls than in controls. Elevation of ghrelin levels remained significant when corrected BMI or corrected BMI Z-score were considered. Unlike in controls, positive correlations were found between ghrelin and age in AIS girls with a gradual increase of circulating ghrelin with age. Conclusions: We have observed significantly higher circulating ghrelin levels in AIS than in controls with a positive correlation with age. This pilot-study suggests that ghrelin signaling might play a role in the initiation or development of AIS. Further studies are needed to validate theses results. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma ghrelin levels have recently been reported in adults and children with Prader-Willi syndrome (PWS). The aim of the study is to investigate the relationship between obesity, growth hormone (GH) deficiency (GHD) and ghrelinemia in PWS and to examine whether hyperghrelinemia is specific to PWS. Methods: We measured fasting ghrelinemia in children with PWS, idiopathic GHD (iGHD), obese children, controls and in 6 children presenting another congenital syndrome associated with GHD: pituitary stalk interruption (PSI). Results: Children with PWS exhibited significantly higher ghrelin levels (995 pg/ml (801/1,099, median 1st/3rd quartile)) than iGHD (517 pg/ml (392/775)), obese (396 pg/ml (145/610)) and control (605 ng/ml (413/753)) children. Similar to PWS hyperghrelinemia was found in PSI children (1,029 pg/ml (705/1,151)), and was not modified by GH treatment. Conclusion: We conclude that hyperghrelinemia in PWS and PSI is not related to GH secretion. We hypothesize that a major site of ghrelin action is at the hypothalamic level and that a ‘ghrelin resistance’ syndrome may be present in these patients, primarily due to a hypothalamic defect. Combined alterations such as impaired serotonin receptor regulation associated with abnormal ghrelin responsiveness are probably responsible for obesity in PWS. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]