Moeder met een missie
Mother with a mission
One small step for Prader Willi Research
One SMALL Step Funded Projects, RFA 1
Question 1: What underlies the shift from failure to thrive to excessive hunger in PWS?
Nutritional Aspects of Prader-Willi syndrome and Childhood Obesity: Correlation of Plasma Orexin Levels with Nutritional Phases
Awarded To: Dr. Jennifer Miller, University Florida
Amount Funded: $20.000,-
Early in infancy, babies with Prader-Willi syndrome (PWS) have no interest in feeding manifested by lack of crying for food and failure-to-thrive requiring assisted feeding with a G-tube, NG tube, or cross-cutting of bottle nipple (phase 1a). There is then a series of transition through five nutritional phases, ending in the classic PWS manifestations of voracious appetite, inability to feel full, food-stealing, taking food from unsavory places such as the garbage can or sink, and obesity (phase 3). Remarkable among the nutritional phases is phase 2a, when the child begins to gain weight rapidly despite no increase in food intake. Individuals with PWS often have excessive daytime sleepiness and sleep abnormalities with early morning awakening typically beginning in phase 2a. Although both problems with sleep and appetite control have been attributed to dysfunction of a specific part of the brain called hypothalamus, to date, there has been no definitive hormonal or metabolic explanation for the brain dysfunction or for the transition from failure-to-thrive to obesity and excessive hunger in PWS. Orexin is a hormone from the brain that promotes wakefulness and appetite. Lack of orexin in the brain has been shown to cause excessive sleepiness and is now thought to cause obesity due to low metabolic rate. Orexin levels in brain fluid have been reported to be low in a few individuals with both PWS and excessive daytime sleepiness, but blood levels have never been studied. We believe that blood orexin levels change over time in individuals with PWS as they transition through the nutritional phases, and that low orexin levels cause excessive sleepiness and obesity by decreasing the metabolic rate. If this study is able to show a relationship between blood orexin levels and the development of obesity and excessive sleepiness, orexin may be a promising medication for individuals with PWS as well as those with other causes of childhood obesity.