Ghrelin levels in children with Prader-Willi syndrome less than six years of age

Christine R. Erdie-Lalena M.D. ¹, Vanja A. Holm M.D. ³, Pat Kelly D.O. ¹, David E. Cummings M.D. ⁴, R. Scott Frayo ⁴, and Troy H. Patience ².

¹Department of Pediatrics, Division of Genetics and Development and ²Department of Clinical Investigation, Madigan Army Medical Center, Fort Lewis, WA;  ³Center of Human Development and Disability, University of Washington, Seattle WA;  ⁴Divison of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle WA

Prader-Willi Syndrome (PWS) is the most common genetic obesity syndrome.  An intriguing progression from failure-to-thrive to morbid obesity occurs between 2 and 6 years of age in these patients.  Ghrelin is a hormone mainly produced in the stomach; which, when given to humans, stimulates appetite and increases food intake. Levels of ghrelin are significantly increased in adults with PWS.  Fasting ghrelin levels have been found to be 3 to 4 fold higher in children 5 to 15 years of age with PWS when compared to obese controls.  Information on ghrelin levels in younger children is not available in the literature.

Objective: The objective of this study was to determine if similar elevations in ghrelin levels occur in children with PWS less then six years of age and not yet obese and at what age those differences occur.

Methods: Subject recruitment was accomplished by self-referral through the Northwest Prader-Willi Syndrome Association newsletter.  After written parental consent had been given, age, height, weight, and time of last meal were determined. The diagnosis of PWS was confirmed by history and chart review when available.  Anthropometric measurements were done by standard methods.  Height (cm) and weight (kg) were used to calculate the Body Mass Index (BMI; kg/m²).  The ghrelin levels were drawn fasting and assayed by the reference laboratory.  Ghrelin levels were analyzed by t test with two samples, equal-variant analysis for statistically significant differences between age/BMI-matched study and control subjects.

Results: There were 14 patients - 7 with PWS and 7 healthy controls.  In the PWS group, all patients had positive methylation studies. One had deletion of 15q by FISH and 6 had negative FISH studies and presumed UPD.  The age of the children with PWS ranged from 18-60 months with a mean age of 39 months.  The age of the control group ranged from 23-69 months with a mean age of 40 months. The BMI’s ranged from 14.0-18.7, with an average of 16.6 in the PWS group; and 14.9-17.4, with an average BMI of 16.2 in the control group.  In PWS, fasting ghrelin levels were not significantly different compared with age/BMI-matched controls (mean +/- SD; 792 +/- 278 vs. 696 +/- 132; P=0.42).  However, statistical significance is approached (P=0.07) when comparing only the UPD PWS.  There was no correlation between age and ghrelin levels in either group.

Conclusions: Unlike adults and older children with PWS, elevation in total ghrelin level was not found in seven non-obese children less than six years of age with PWS when compared to age mates. The reason for this discrepancy is unclear. The sample size is small and we are presently planning to increase the size of the study. Elevated levels of ghrelin in obese persons with PWS is an important finding that, if treatable, promises a better outlook for the quality of life for individuals with this condition. Additional studies in younger children with PWS are needed to better understand ghrelin’s role in appetite and eating behaviors in PWS. 

June 2004