IPWSO Zurich Conference Report October 2002

Prader-Willi syndrome as a model for obesity

Editors: Urs Eiholzer, Dagmar l’Allemand, William B. Zipf

Almost fifty years ago, in 1956, three Professors at the University of Zurich, Andrea Prader, Alexis Labhart and Heinrich Willi, first described what is now called Prader-Willi syndrome (PWS). The study and the therapy of this syndrome has progressed so rapidly in the past years that the decision was made to share recent advances with the scientific community and to address topics of future research at an international meeting. Results of this meeting are presented in this book.

It is becoming increasingly obvious that PWS is a multi-systemic disorder. Improving living conditions of patients and their families therefore requires broad professional support. While growth hormone therapy influences growth and body composition, many other problems such as insufficient satiation, hypoactivity, behavioural difficulties, speech problems and mental retardation remain to be addressed. Psychological support is needed to help parents in their battle against the eating disorder and the behavioural problems of their child. Thus, a comprehensive team approach will yield the best results for both patients and parents. PWS research may also contribute to basic medical research by providing new insights into the metabolism of other obese patients. In this way, PWS may be used as a model for obesity.

The rare Prader-Willi syndrome (PWS), a genetic disease resulting in obesity in one out of 10’000 newborns, represents a good candidate to enable better understanding of the molecular control of energy homeostasis in humans, according to Columbia University professor Rudolph L. Leibel. In October 2003, 130 scientists from all over the world gathered in Zurich to discuss how the well-being of patients with Prader-Willi syndrome can be improved through an interdisciplinary approach, and how the disease itself might be utilized as a model to extend our understanding of the regulation of body weight and composition.

PWS results from a paternally derived deletion or an imprinting defect on chromosome 15. Patients with PWS suffer from muscle weakness, feeding problems and developmental delay during the first two years and from obesity, short stature, hypogonadism and behaviour problems thereafter. At about two years of age patients with Prader-Willi syndrome develop a nearly insatiable appetite. Without vigorous control, even teenagers can gain up to 300 kg in weight. Morbidity, mortality and quality of life of patients with PWS are mainly depending on weight control and body composition. Current therapies therefore include strict dietary control, increased physical exercise and substitution with growth hormone to improve body composition and height.

Scientists from a number of disciplines including genetics, paediatrics, endocrinology, psychiatry and nutrition exchanged their views, observation and research results on PWS and arrived at the conclusion that patients with PWS, despite their obesity, show many signs that are characteristic of starvation. “For our for-bearers the problem was how to get enough fat and to hang on to it”, said Rudolph Leibel in his closing remarks. “Thus, a number of genes are responsible for gaining body fat. The problem of excess body fat has probably been rare or non-existent in evolution. Therefore, there are very few, if any, genes, which are designed to suppress body fat. In PWS, a gene is missing that plays a very important role in the defence of body fat. This loss causes the body to sense that it might not have adequate fat mass and energy stores. Identification of the gene(s) responsible for the Prader-Willi syndrome might reveal a new pathway in the regulation of body weight.”