Original article
Ghrelin levels in young children with Prader-Willi syndrome

https://doi.org/10.1016/j.jpeds.2006.04.011Get rights and content

Objective

To explore the hypothesis that high ghrelin levels contribute to obesity in Prader-Willi syndrome (PWS), we assessed whether the increased levels observed in older persons with PWS exist in very young children, before the onset of hyperphagia.

Study design

We measured ghrelin levels in nine children with PWS (17-60 months of age) and eight healthy control subjects of equivalent body mass index (BMI), age, and sex.

Results

PWS and control groups had equivalent BMI (16.8 ± 1.4 vs 16.1 ± 0.9 kg/m2, respectively; P = .24), age (37.8 ± 15.4 vs 50.3 ± 17.7 months; P = .14), and sex. PWS and control groups also had equivalent fasting levels of total ghrelin (787 ± 242 vs 716 ± 135 pg/mL, respectively; P = .24), bioactive ghrelin (102 ± 35 vs 91 ± 23 pg/mL; P = .45), insulin, and glucose. Ghrelin correlated negatively with BMI among controls (r = −0.760, P = .029) but not PWS (r = 0.015, P = .97).

Conclusions

Children <5 years of age with PWS, who had not yet developed hyperphagia or excessive obesity, had normal ghrelin levels, in contrast with the hyperghrelinemia of older, hyperphagic people with PWS. It is possible that ghrelin levels increase suddenly before hyperphagia develops.

Section snippets

Subjects

This study was approved by the Human Subjects Research Division at the University of Washington. A recruitment letter was published in the Northwest PWS Association Newsletter, and interested families contacted the principal investigator to review the protocol.

After written parental consent and assent (for verbal children) were obtained, age, height, weight, and time of the last meal were determined. The diagnosis of PWS was confirmed by history and chart review. There were nine children with

Results

We studied nine patients with PWS and eight healthy control subjects, who were either related to or close friends of the children with PWS, and who were of equivalent age, BMI, and sex (Table). In the PWS group, all patients had positive studies for methylation of genes in the PWS locus, confirming their diagnosis. One child had a deletion of 15q documented by fluorescence in situ hybridization (FISH), and eight had negative FISH studies and presumed uniparental disomy. There were three sibling

Discussion

Children <5 years of age with PWS did not display significant elevation of total or acylated plasma ghrelin levels, when compared with controls of equivalent age, BMI, sex, and levels of insulin, glucose, and insulin sensitivity. These results differ from those reported previously in obese adults with PWS (mean BMI ± SD of 33.9 ± 9.0)25 and in obese children with PWS who were 5 to 16 years of age.30, 32, 33 In these prior studies, people with PWS had elevated plasma ghrelin levels. One

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    Supported by NIH grants RO1 DK61516 and PO1 DK68384 (to D.E.C.).

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