Ghrelin in young kids with PWS- waiting for the storm?

A new paper out in the Journal of Pediatrics looks at Ghrelin levels in young children with Prader-Willi syndrome - Erdie-Lalena CR, Holm VA, Kelly PC, Frayo RS, Cummings DE. J Pediatrics, 149:199-204, 2006). This study adds to the existing literature on ghrelin in PWS, and raises the possibility that ghrelin in low is young children with PWS, but increases with age. The authors find that in contrast to earlier studies done in adults with PWS (done by this group and others), ghrelin was not significantly higher in the group of young children (5 and under) with PWS studied here compared to matched controls without PWS. As has been noted before, including by this group, there is a large variation between individuals with respect to the levels of circulating ghrelin (both active and total). For the kids with PWS in this study, the average level of total ghrelin was 787, but the levels went up to >1000 pg/mL, whereas in kids without PWS, the levels were not above 851. So, even though statistically-speaking, the young children with PWS were not ‘different’, there was a trend towards ghrelin being higher in kids with PWS, and much more variation in the PWS kids compared to the controls. In adults with PWS you see some of the same thing – not all adults with PWS have ghrelin levels above normal- some normals, some elevated, and some very, very high. This study is from one of the most knowledgeable labs studying PWS and ghrelin, but a limitation of the study is its small sample size (9 kids with PWS, 8 controls). A different study a couple of years ago looked at 39 people with PWS, including about 20 under the age of 5. They found just the opposite: a trend towards decreased ghrelin in older compared to younger children (see that article here). If you look at their data, however, you can see the variation between individuals, making it hard to draw conclusions about age-related changes in ghrelin levels. Finally – and this is probably very important - a major difference between this study and most others is that almost all the individuals with PWS in this study (8 of the 9) had PWS due to uniparental disomy. Since some aspects of PWS tend to be milder in UPD, this characteristic of the study population may account for the low ghrelin levels. It’s important to note that not all parents see a ‘sudden onset’ of hunger at age 2 (or 5 or 6), which is often referred to in the PWS literature. For some, their children never seem full, but don’t express a constant hunger that increases with age. What is really needed, as the authors themselves point out, is a study that follows ghrelin levels over time to see if the low levels here are just a consequence of the particular individuals that were enrolled in the study, or really do represent the ‘calm before the storm’. If their hypothesis is true, you would expect kids with relatively low ghrelin to have a ‘jump’ in levels with the onset of increased appetite. No doubt there's more to come on this topic.....