Elevated ratio of acylated to unacylated ghrelin in children and young adults with Prader–Willi syndrome

Prader–Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. Hyperghrelinemia may be involved in the underlying mechanisms of the switch. The purpose of this study is to evaluate acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in PWS and investigate their associations with hyperphagia. This is a cross-sectional clinical study conducted in three PWS expert centers in the Netherlands and France. Levels of AG and UAG and the AG/UAG ratio were determined in 138 patients with PWS (0.2–29.4 years) and compared with 50 age-matched obese subjects (4.3–16.9 years) and 39 healthy controls (0.8–28.6 years). AEBSF was used to inhibit deacylation of AG. As a group, PWS patients had higher AG but similar UAG levels as healthy controls (AG 129.1 vs 82.4 pg/ml, p = 0.016; UAG 135.3 vs 157.3 pg/ml, resp.), resulting in a significantly higher AG/UAG ratio (1.00 vs 0.61, p = 0.001, resp.). Obese subjects had significantly lower AG and UAG levels than PWS and controls (40.3 and 35.3 pg/ml, resp.), but also a high AG/UAG ratio (1.16). The reason for the higher AG/UAG ratio in PWS and obese was, however, completely different, as PWS had a high AG and obese a very low UAG. PWS patients without weight gain or hyperphagia had a similar AG/UAG ratio as age-matched controls, in contrast to those with weight gain and/or hyperphagia who had an elevated AG/UAG ratio. The switch to excessive weight gain in PWS seems to coincide with an increase in the AG/UAG ratio, even prior to the start of hyperphagia

Le syndrome de Prader-Willi en 2015

Le syndrome de Prader-Willi est un trouble du développement lié à un défaut d’expression de gènes de la région 15q11-q12 soumise à une empreinte parentale maternelle. Le diagnostic peut aujourd’hui être porté très tôt, ce qui permet de décrire l’histoire de la maladie et, en particulier, les phases nutritionnelles allant de difficultés alimentaires sévères en période néonatale jusqu’à l’apparition d’une obésité morbide avec hyperphagie et déficit de satiété. S’associent des dysfonctionnements endocriniens, un déficit cognitif modéré, des troubles des apprentissages, des troubles du comportement et des habilités sociales, et des troubles psychiatriques. La prise en charge multidisciplinaire a été fortement développée grâce à la mise en place du plan Maladies rares en 2004 et du plan Obésité en 2011, en lien avec l’association des familles (Prader-Willi France). Des perspectives thérapeutiques physiopathologiques intéressantes existent aujourd’hui

Apprendre les émotions aux enfants porteurs d’un syndrome de Prader-Willi : le programme EMOT

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Equivocal expression of emotions in children with Prader-Willi syndrome: what are the consequences for emotional abilities and social adjustment?

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Face processing and exploration of social signals in Prader-Willi syndrome: a genetic signature

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A study of voice and non-voice processing in Prader-Willi syndrome

International audiencePrader-Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder of genetic origin. Itmanifests itself in endocrine and cognitive problems, including highly pronounced hyperphagia and severe obesity.In many cases, impaired acquisition of social and communication skills leads to autism spectrum features, andindividuals with this syndrome are occasionally diagnosed with autism spectrum disorder (ASD) using specificscales. Given that communicational skills are largely based on vocal communication, it is important to study humanvoice processing in PWS.We were able to examine a large number of participants with PWS (N = 61) recruited from France’s nationalreference center for PWS and other hospitals. We tested their voice and nonvoice recognition abilities, as well astheir ability to distinguish between voices and nonvoices in a free choice task. We applied the hierarchical driftdiffusion model (HDDM) with Bayesian estimation to compare decision-making in participants with PWS andcontrols. We found that PWS participants were impaired on both voice and nonvoice processing, but displayed acompensatory ability to perceive voices. Participants with uniparental disomy had poorer voice and nonvoiceperception than participants with a deletion on chromosome 15. The HDDM allowed us to demonstrate thatparticipants with PWS need to accumulate more information in order to make a decision, are slower at decision-making, and are predisposed to voice perception, albeit to a lesser extent than controls. The categorization of voices and nonvoices is generally preserved in participants with PWS, thoughthis may not be the case for the lowest I

Interference effect of food and emotional stimuli in Stroop-like tasks for children and adults with Prader-Willi Syndrome

International audienceInterference effect of food and emotional stimuli in Stroop-like tasks for children and adults with Prader-Willi Syndrome. The aim of this work was to study the way items related to food or emotion are processed by a population known to have difficulties with dietary restriction, namely individuals with Prader-Willi Syndrome (PWS). Given the presence of intellectual disability (ID) in PWS, our experiments were designed to examine whether these difficulties were specific to PWS or linked with their ID. Two modified Stroop tasks (i.e., a food version and an emotional version) were administered to seventy-four children (aged between 6 and 16 years old) divided into three groups (one with PWS, one with ID matched on age and Intellectual Quotient (IQ), and one healthy group matched on age) and to eighty-four adults (aged between 18 and 48 years old) distributed in the same three groups. For both tasks, a picture version was used for the children and a word version for the adults. For the food Stroop task, (Experiment 1), materials were composed of low or high-caloric food items and stimuli not related to food. The results show a food Stroop effect for children and adults with PWS that was absent in the group of healthy participants. Moreover, a food Stroop effect was also significant for adults with ID. For the emotional Stroop task (Experiment 2), materials were composed of negative, positive and neutral stimuli. The emotional Stroop effect was also obtained for children and adults with PWS as well as for the healthy group, but not for the age- and IQ-matched group. For the PWS groups, results show a preservation to process positive pictures for children and difficulties to process negative stimuli for both age-groups. These results suggest that people with PWS have difficulties in disengaging their attention when food stimuli are present in their environment and poorer abilities to process negative ones. These difficulties endure in adulthood

Towards optimal treatment with growth hormone in short children and adolescents: evidence and theses

Treatment with growth hormone (GH) has become standard practice for replacement in GH-deficient children or pharmacotherapy in a variety of disorders with short stature. However, even today, the reported adult heights achieved often remain below the normal range. In addition, the treatment is expensive and may be associated with long-term risks. Thus, a discussion of the factors relevant for achieving an optimal individual outcome in terms of growth, costs, and risks is required. In the present review, the heterogenous approaches of treatment with GH are discussed, considering the parameters available for an evaluation of the short- and long-term outcomes at different stages of treatment. This discourse introduces the potential of the newly emerging prediction algorithms in comparison to other more conventional approaches for the planning and evaluation of the response to GH. In rare disorders such as those with short stature, treatment decisions cannot easily be deduced from personal experience. An interactive approach utilizing the derived experience from large cohorts for the evaluation of the individual patient and the required decision-making may facilitate the use of GH. Such an approach should also lead to avoiding unnecessary long-term treatment in unresponsive individuals

Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity

CONTEXT: Prader-Willi syndrome (PWS) is characterized by lack of appetite control and hyperphagia, leading to obesity. Pharmacological options for weight management are needed. OBJECTIVE: To determine whether liraglutide treatment for weight management is superior to placebo/no treatment in pediatric individuals with PWS. METHODS: This was a multicenter, 52-week, placebo-controlled trial with a 16-week double-blinded period. Adolescents (n = 31, aged 12-17 years; Tanner stage 2-5) and children (n = 24, aged 6-11 years; Tanner stage <2) with PWS and obesity were included. Patients were randomized 2:1 to liraglutide 3.0 mg (or maximum-tolerated dose) or placebo for 16 weeks, after which placebo was stopped. Liraglutide was continued for 52 weeks. All patients followed a structured diet and exercise program throughout the trial. The coprimary endpoints were change in body mass index (BMI) standard deviation score (SDS) from baseline to 16 and 52 weeks. Secondary endpoints included other weight-related parameters, hyperphagia, and safety. RESULTS: Change in BMI SDS from baseline to weeks 16 and 52 was not significantly different between treatments in adolescents (estimated treatment difference: -0.07 at week 16 and -0.14 at week 52) and children (-0.06 and -0.07, respectively). Changes in other weight-related parameters between treatments were not significant. At week 52, hyperphagia total and drive scores were lower in adolescents treated with liraglutide vs no treatment. The most common adverse events with liraglutide were gastrointestinal disorders. CONCLUSION: Although the coprimary endpoints were not met, changes in hyperphagia total and drive scores in adolescents warrant further studies on liraglutide in this population