Assessment of Energy Expenditure in Prader-Willi Syndrome: Comparison with Obese Subjects            

Merlin G. Butler¹, Douglas C. Bittel¹, Zohreh Talebizadeh¹, Joseph E. Donnelly², Travis Thompson³

¹Section of Medical Genetics and Molecular Medicine, Children's Mercy Hospitals and Clinics and University of Missouri-Kansas City School of Medicine, Kansas City, MO ²Center for Physical Activity and Weight Management, University of Kansas, Lawrence, KS ³ Minnesota Autism Center, Minneapolis, MN

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder characterized by hypotonia, poor suck and feeding difficulties, hypogonadism, small hands and feet, developmental delay, hyperphagia and early childhood obesity and a particular facial appearance.  A de novo paternal deletion of 15q11-q13 accounts for approximately 70% of PWS cases, about 25% of cases are due to maternal disomy 15 and the remaining cases are due to disruption of the imprinting center or chromosome 15 rearrangements.

The obesity associated with PWS is the result of a chronic imbalance between energy intake and energy expenditure (EE) due to hyperphagia, decreased physical activity, reduced metabolic rate and an inability to vomit. EE is affected by body composition as well as exercise. PWS subjects have a lower fat free mass compared with controls which may contribute to reduced basal level energy expenditure. To determine the relationship among body composition data, activity levels and metabolic rates, dual energy X-ray absorptiometry (DEXA) and a whole room respiration chamber were used to measure body composition, total EE, resting EE and physical activity during an 8 hour monitoring period. The chamber consisted of a live-in whole-room indirect calorimeter equipped with a force platform floor to allow simultaneous measurement of EE, physical activity and work efficiency during spontaneous activities and standardized exercise.  

	PWS (n = 49)	Obese (n = 27)
Sex (M/F)	22/27	10/17
Age, Yrs + SD (range)	22 + 8 (10-44)*	27 + 13 (11-49)
BMI + SD (kg/m2)	34 + 9*	39 + 9
% Fat + SD	50 + 7**	45 + 9
Total EE + SD (kcal/day)	2134 + 405 ***	2598 + 666
Resting EE + SD (kcal/day)	1762 + 372 ***	2125 + 532
Total Mechanical Work (kcal/day)	30 + 14 *	46 + 33

Difference is statistically significant  * p< 0.05, ** p< 0.01, ***p < 0.001

PWS subjects (27 deletion, 21 maternal disomy, 1 imprinting center defect) had significantly decreased total EE by 18% compared to obese comparison subjects (p < 0.001).  Similarly, resting EE was significantly reduced by 17% in the PWS subjects relative to the comparison subjects (p < 0.001).  Total mechanical work performed during the 8 hour monitoring period was significantly reduced by 35% in the PWS group (p < 0.05).  The energy cost of physical activity is related to the duration, intensity and type of the activity and the metabolic efficiency of the individual.  After adjusting group differences in lean body mass by analysis of covariance, total EE and resting EE were no longer different between the two groups. Our data indicate that there is a significant reduction of energy expenditure in subjects with PWS resulting from reduced activity but also from lower energy utilization due to reduced lean body mass.