Effect of Somatostatin on Ghrelin Concentrations, Food Seeking Behaviour and Weight in Patients With Prader-Willi Syndrome

Prader-Willi Syndrome and Obesity:

Prader-Willi syndrome (PWS) is a genetic disorder occurring in 1/10,000 to 1/15,000 live births. Clinical characteristics include neonatal and infantile central hypotonia with feeding problems and poor weight gain followed after 1-3 years by hyperphagia and excessive weight gain. Patients also have characteristic facial features, short stature (possibly due to growth hormone [GH] deficiency of hypothalamic origin), hypogonadism, increased pain threshold, global developmental delay and variable mental retardation.

Obesity is clearly one of the cardinal features of PWS. It can result in tremendous distress for both the parents and the affected child and is a significant health problem with complications that include hypertension, sleep apneas and diabetes. More than 1/3 of patients with PWS weigh more than 200% of their ideal body weight. Obesity is thought to result mainly from hyperphagia, persistent hunger with increased caloric intake, decreased perception of satiety and obsessive and compulsive behaviours that are primarily food related. Decreased physical activity associated with hypotonia and/or decreased energy expenditure is also thought to play a role in the pathophysiology of obesity.

The treatment of obesity in PWS is very difficult and requires constant involvement of the parents or caregivers with establishment of rigid structures around the young patient: increased physical activity, hiding food, locking fridges etc. Recently, studies on the effects of growth hormone (GH) treatment (now an approved indication in most patients with PWS in the US irrespective of their GH status) on body composition in PWS have been performed. While GH, among other favourable effects, significantly improves body composition (increased lean mass and decreased fat mass), the long-term effects on body mass index are modest and variable.

Thus, obesity is clearly one of the greatest challenges faced by parents of patients with PWS and treatment modalities are presently not successful.