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 DOI: 10.1177/1941406409348555

2009 1: 282ICAN: Infant, Child, & Adolescent NutritionRosanna Pereira, Angela Schalk and Maureen E. Geraghty

Prader-Willi Syndrome A Review for Pediatric Nutrition Professionals  

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ICAN: Infant, Child, & Adolescent Nutrition October 2009

282

Prader-Willi SyndromeA Review for Pediatric Nutrition ProfessionalsRosanna Pereira, Angela Schalk, and Maureen E. Geraghty, PhD, RD, LD

Review of Resources

DOI: 10.1177/1941406409348555. From the Department of Medical Dietetics, School of Allied Medical Professions, The Ohio State University, Columbus. Address for correspondence: Maureen E. Geraghty, PhD, RD, LD, Division of Medical Dietetics, School of Allied Medical Professions, College of Medicine, The Ohio State University, 453 W 10th Avenue, 306 L Atwell Hall, Columbus, OH 43210; e-mail: Maureen.geraghty@osumc.edu.

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Copyright © 2009 The Author(s)

Abstract: Prader-Willi syndrome is a complex, multidimensional disease affecting approximately 1 in 8000 to 1 in 50 000 individuals. Although there is an abundance of data available regard-ing Prader-Willi syndrome, there are few sources of compiled, nutritionally pertinent information. Nutrition inter-vention is currently the only treatment for Prader-Willi syndrome, and there-fore it is critical that nutrition profes-sionals have an understanding of the disease. This review provides back-ground information regarding Prader-Willi syndrome and the causes of obesity and hyperphagia, as well as outlines current nutritional recommendations and strategies for working with individ-uals with Prader-Willi syndrome. It is recommended that the diet of these chil-dren be strictly controlled and struc-ture provided, yet it is important to allow for some flexibility to enhance quality of life. Behavioral issues also need to be considered as they render it a challenge for parents to impose restrictions on their children’s eating patterns.

Keywords: endocrine and metabolism; developmental disabilities; growth prob-lems; special health care needs; Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a genetic disorder that results from chromosomal abnormalities. The

symptoms of PWS can be devastating to the child and the family, both physically and emotionally. The prevalence has been reported to be anywhere from 1 in 8000 to 1 in 50 000, and although PWS is a lifelong disease, it is often consid-ered a pediatric issue because of the age of diagnosis and the difficulty manag-ing the disease in childhood.1 As integral members of an interdisciplinary team, it is critical that nutrition professionals understand the complexity of this dis-ease. Currently, nutrition professionals play a major role in the management of PWS, as dietary restriction is one of the only successful treatments. However, it is not enough to simply recommend energy restriction; nutrition professionals must be prepared to offer creative strat-egies to ensure that nutrition care plans become a reality. The purpose of this article is to provide a thorough outline of Prader-Willi syndrome, including the emotional and quality-of-life issues sur-rounding PWS, as well as provide spe-cific recommendations as to what nutri-tion professionals can do to support these families, both nutritionally and otherwise.

Etiology and Diagnosis of Prader-Willi Syndrome

About 75% of PWS cases are due to a band deletion on paternal chromosome 15.1 Twenty-four percent of PWS cases arise from maternal disomy of the 15th chromosome,1 meaning that both chromo-somes in the pair come from the mother. The final 1% of PWS cases are caused by an imprinting error on the paternal 15th chromosome.1 It is interesting to note that when these deletions and mutations occur on the maternal 15th chromosome, it results in Angelman syndrome.

Prenatal diagnosis is not typically rec-ommended, but in rare cases, it is per-formed via amniocentesis. This is usually only done if PWS is suspected because of reduced fetal movements and polyhydroamnios.1,2 Otherwise, PWS is diagnosed after birth based on the pre-sentation of various signs and symptoms such as a thin upper lip, almond-shaped eyes, small hands and feet, genital hyp-oplasia, and hypotonia. It is then con-firmed by genetic testing.1 Of the clinical signs, hypotonia is the most evident at birth; in fact, one study found that 100% of the newborns with PWS in the study presented with hypotonia at birth.3 This same study found that early diagnosis of

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PWS can decrease the duration of tube feeding and also decrease hospital stay. Because there are such positive bene-fits of early diagnosis, it is recommended that every child who presents with hypo-tonia at birth should be genetically tested for PWS.3

Stages of Prader-Willi Syndrome

Stage 1: Failure to Thrive

The first stage of PWS typically con-sists of failure to thrive (FTT) throughout infancy. At birth, infants with PWS actu-ally tend to be of normal length and are either normal weight or underweight.1,4 Infants with PWS do, however, present with generalized hypotonia at birth, often affecting the oral cavity, which com-monly leads to a poor sucking ability. This, in turn, leads to FTT.

Breast milk should be offered, but because of poor suck, breastfeed-ing may not be optimal. Families that wish to breastfeed may find it helpful to work with a certified lactation consul-tant. Another option is to give expressed breast milk or formula by bottle, but this may also present a challenge for infants with PWS again due to poor suck.5 If the baby cannot adequately suck from a bottle, a variety of modified nipples are available to adjust the flow. Cutting the nipple is generally not recommended as issues with increased milk flow and bac-teria may become problematic.

Even with the availability of modified nipples, it is not unusual that infants born with PWS require tube feeding to receive adequate nutrition. It should be noted that the combination of prolonged tube feeding and the absence of oral feeding can theoretically contribute to the already impaired speech ability in many infants with PWS down the road.1 Interventions with health care professionals such as a speech language pathologist or occu-pational therapist may be beneficial to support and enhance both feeding and speech skills for the future. Regardless of the source of calories, the goal is for the infant to be kept between the 50th and 75th percentile of his or her weight for height to ensure proper growth with-

out the promotion of overweight, which is the goal for infants with PWS.5 Careful weight and length records should be maintained so that weight for length can be constantly reevaluated. If applica-ble, the Centers for Disease Control and Prevention (CDC) growth charts for low birth weight infants should be used.6 The basal metabolic rate for those with PWS is slower even at birth, and there-fore infants with PWS require fewer cal-ories than a typical infant to maintain a healthy weight. For this reason, prac-titioners must use caution when calcu-lating nutrition needs, regardless of the feeding method, as the traditional meth-ods (based on weight) may overestimate the actual needs. Recommendations for feeding regimens during infancy will be provided.

Stage 2: Hyperphagia

The second stage of Prader-Willi syn-drome is marked by excessive weight gain and an increased interest in food. This phase can begin as early as 18 months to 3 years of age. In some cases, the aggressive food-seeking behaviors are not seen until as late as 15 years.1 It is not uncommon for individuals with PWS to seek and ingest nonfood items (paper, playdough, lotions) as well. Although the exact etiology of the hyper-phagia is unknown, there have been observed abnormalities in appetite- related hormone feedback systems. It has been repeatedly observed and reported that both children and adults with PWS have elevated levels of the appetite- stimulating hormone, ghrelin, and decrea-sed levels of the appetite-suppressing hormone, pancreatic polypeptide.1,7-11 This leads to constant feelings of hunger even after a meal is consumed. Unfortunately, even upon administration of somatosta-tin, which significantly suppresses ghre-lin levels, there is no effect on appetite in those with PWS, so the child still feels hungry.1 At this point, the exact role and mechanism of these hormones remain unclear, and more research is needed. There is also evidence that, in those with PWS, the regions of the brain that should provide feelings of satiety are actually insensitive, even to high-volume food

intake.12 It has been shown that those with PWS need to eat about 3 times as much as the typical person to feel sati-ated, and they then begin to feel hun-gry again sooner, even after consuming an increased amount of calories.1,13 This occurs despite evidence of delayed gas-tric emptying in those with PWS.

Because of the increased appetite, it has been traditionally thought that those with PWS eat large amounts of food indis-criminately. However, a 2002 study con-ducted by Joseph et al14 found that this is somewhat of a misconception. This study concluded that if an individual with PWS is presented with a small amount of a desirable food available immedi-ately but knows a greater amount of a less desirable food will be available later, he or she will forego the immediate con-sumption of food in favor of the greater quantity in the future.14 The study dem-onstrated that choices by those in the PWS study group were more likely to be guided by food quantity than those who were in the “obese” non-PWS compari-son study group. These results may be useful in practice when managing eating behaviors.

Nutrition and Dietary Management of Prader-Willi Syndrome

Energy Expenditure

In addition to diminished satiety, those with PWS also have a decreased meta-bolic rate both when resting and when active. This is the case even at birth, and it can be attributed to skewed body com-position. In those with PWS, body fat generally makes up about 40% to 50% of their total body composition, 2 to 3 times higher than the general popula-tion.15 This leads to a lower resting meta-bolic rate because lean body mass is the more metabolically active tissue. Not only do those with PWS have an increased fat mass, but their ability to metabolize fat is decreased as well. One study found that fat oxidation in a group of individuals with PWS was 37% lower than a group of obese individuals without PWS.15 This same study found that those with PWS have less spontaneous movement, more

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severe hypotonia, and compromised muscle coordination, which would make it particularly challenging to participate in exercise and physical activity.

Recent literature provides 3 studies that have measured the energy expendi-ture of those with PWS. The first study, performed by Bekx et al4 in 2003, mea-sured the daily energy expenditure of 16 infants and toddlers with PWS (aver-age age, 12.4 months; SD, 6 months). It was reported in this study that the aver-age daily energy expenditure was 587 kcal. This corresponded with an energy requirement of about 71 kcal/kg based on the mean weight of the children in the study, almost 30% lower than the cur-rent recommendation of about 100 kcal/kg for a typical child this age.16 A second study that measured energy expenditure in 17 children and adolescents with PWS (mean age, 11.3 years; SD, 3.4 years) reported that the average daily meta-bolic rate (ADMR) in those with PWS was 1705 kcal/d (34 kcal/kg) compared to an ADMR of 2374 kcal/d (39 kcal/kg) in the obese control group with a sta-tistically similar weight. This study also found that, per kilogram of body weight, activity-related energy expenditure (as opposed to calories burned at rest) was about 50% lower in the PWS participants. It was unclear, however, if this were due to decreased energy expenditure dur-ing activity or simply a lower activity lev-el.17 It is of note that although the basal metabolic rate (BMR) of those with PWS was found to be significantly lower than the control group, this significance dis-appeared when BMR was adjusted for percent fat-free mass. Therefore, much of the disparity in metabolic rate can be attributed to the differences in body composition.

A third study, which looked at the energy expenditure of 48 individuals with PWS, found similar results. Compared with the control group, those with PWS had a 20% lower total energy expendi-ture, a 16% lower resting energy expendi-ture, and a 38% lower energy expenditure during physical activity. Once again, the significant differences in total energy expenditure were erased when corrected for percent fat-free mass.15 Although this

study was not performed specifically on the pediatric population, there were no significant differences found between those older than 13 years of age and those younger than 13 years of age. The authors concluded that this significant reduction of energy expenditure in per-sons with PWS is the result of reduced activity and lower energy use due to reduced lean body mass (LBM), which consists primarily of muscle.15

Recommendations for Energy Intake

A general guideline given for preschool and school-age children with PWS is 10 to 11 calories per centimeter of length to maintain weight and 8 to 9 calories per centimeter to lose weight.16 Another rec-ommendation that has been made is for young children to aim for about 600 to 800 calories per day and for older chil-dren and adults to aim for 800 to 1100 calories per day.5 Although these rec-ommendations may seem low, it has

been reported that energy requirements for weight maintenance are 50% to 75% lower in those with PWS versus non-PWS individuals.18 These guidelines pro-vide a starting point for calculating energy requirements, but the patient’s weight should be assessed frequently and the energy intake adjusted accord-ingly. Growth charts specific for the PWS population are available in the Pediatric Manual of Clinical Dietetics published by the American Dietetic Association,16 but these growth charts should be used in conjunction with the CDC growth charts as the PWS-specific charts are based on a limited sample size.6 Detailed food logs are useful and recommended, especially upon the initiation of a new diet regi-men.19 They allow the nutrition profes-sional to accurately assess caloric intake, as the family may not be able or will-ing to calculate intake as thoroughly as is necessary. Ideally, the calories ingested would come from nutrient-dense foods

because the calorie restrictions lead to limited opportunities for nutrient consump-tion. However, behavioral and quality- of-life issues do need to be taken into consideration. A diet that has no opportu-nity for the occasional “treat” may prove to be more difficult than the parents or child can manage. As often discussed, it is best for these “treats” to be planned so that the diet still provides structure with-out being too overwhelming for the fam-ily to handle. In addition, it is important for all those with PWS to take a multivi-tamin to compensate for the vitamin and mineral intakes that may be suboptimal because of the restrictive diet.16

Behavioral Issues

The hyperphagia seen in children with PWS, combined with developmental problems, can lead to an array of behav-ioral issues. Many times these behavioral problems are related to the severe diet restrictions placed on children with PWS; tantrums are common after children

are told they cannot eat the food they desire. Although it is not uncommon that behavioral problems present a con-stant struggle for the parents, strategies can be used to help alleviate some of the tantrums. One strategy that a recent study found may be successful is prom-ising more desirable food later to pre-vent immediate food consumption. For example, if a child sees potato chips in the store that he or she would like to eat immediately, the parent may say, “If you do not eat those chips right now you will be able to have a pudding cup after din-ner.” This should not be used to reward good behavior with food but rather to prevent food consumption at spontane-ous times throughout the day.14 At first this strategy may be difficult to imple-ment, as delayed gratification is often a hard concept to grasp. However, by working with a registered dietitian, fam-ilies may find the support and guidance needed to be successful.

“Managing PWS is certainly difficult but can be rewarding with the proper support and guidance.”

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Other studies have found that people with PWS actually come to prefer a food-controlled environment.1,20 Structure is critical when managing behavioral issues, both in the meals themselves and in the enforcement of the diet.20 For example, meals should fall at the same time each day, and portion sizes should be consis-tent. Also, as hard as it may be on the parents at first, children should not be allowed to stray from the diet, and they should receive consequences each and every time they break the rules. In this same spirit, parents should reward their child for good behavior, although these rewards should not be food. Keep in mind the diet may include some “treats” occasionally, which are to be allowed as long as they are part of the complete diet prescription. Another strategy that has been somewhat successful is to involve the child in his or her diet and food choices.20 This entails allowing the child to help choose a menu or assist in pre-paring the meal. Because it naturally pro-vides structure while still allowing for some flexibility, the exchange system is often used as a meal plan for individu-als with PWS. This puts the emphasis on food groups and portion sizes and lets the child (with his or her parent) choose which foods he or she would like to eat for each exchange.

All of these strategies should help to moderate the behavior of a child or ado-lescent with PWS by providing structure and control in the life of that individual. Additional information on behavior man-agement beyond the scope of this article can be found in Prader-Willi Syndrome: Selected Research and Management Issues by Caldwell and Taylor.21

Controlling Weight Gain and Excessive Eating

Although it may be difficult for the parents, it is important that refrigera-tors, cupboards containing food, and even garbage cans remain locked once the child is old enough to access these locations.19 Parents need to explain the importance of food restriction to others with whom their child might stay, such as grandparents or a friend. It is also impor-tant that the caregiver or nutrition profes-

sional weighs the child routinely so that weight gain can be monitored closely. These weigh-ins should ideally occur weekly and, at a minimum, monthly.22

Many other strategies for managing hyperphagia in PWS have been devel-oped and used, such as using smaller serving dishes, cutting food into smaller pieces, and keeping healthy, low-calorie snacks around the house. Additional strategies are discussed in Greenswag and Alexander’s Management of Prader-Willi Syndrome.5 Not every suggestion will work for every family, but most will be able to find strategies that work. It is the job of the nutrition professional to provide suggestions, encouragement, and support to these families while exploring successful nutrition strategies.

Other Treatments

Growth Hormone

Unfortunately, at this time, there are no medications that have been found to sup-press the aggressive appetite of those with Prader-Willi syndrome.1,7 However, there have been some promising results with the use of growth hormone (GH), which has been reported to accelerate linear growth, increase energy expendi-ture, and improve body composition.23 Although most newborns with PWS appear to be normal length, by the sec-ond or third year of life, there seems to be a decrease in growth velocity. This is usually attributed to GH deficiency, a common problem for children with PWS. One study found that if GH was adminis-tered before puberty, it would normalize the child’s height.24 In this same study, growth hormone was also shown to decrease fat mass and weight for height; however, in this particular study, the GH treatments did not normalize lean body mass. A second study also found that GH had a positive impact on final adult height, with adult height being nega-tively correlated with age at initiation of treatment.23 This study also compared the final adult height of individuals with PWS who were treated with GH to a control group of individuals with PWS who did not have GH treatment. The study found a significant difference in the heights of

individuals treated with GH compared to the control group—67 versus 61 inches in males and 62 versus 56 inches in females.23

Much of the literature shows benefits when beginning GH treatment as early as 2 years of age. There is also evidence of additional benefits, including improved motor development and cognition, if treatment is initiated in children as young as 6 months to 1 year of age.1 However, in the United States, GH is only labeled for short stature, so it is often difficult to gain approval for this treatment at such a young age.1

Although GH has shown to have many benefits for those with PWS, its side effects cannot be overlooked. GH is known to cause respiratory problems for some, and it has caused deaths due to bronchopneumonia, respiratory insuffi-ciency, and sleep apnea.25 For this rea-son, those with PWS should have a thorough sleep study and upper respira-tory examination conducted before start-ing GH treatment. Other side effects may include scoliosis and hyperglycemia.25 It is important to note that those with PWS, who are likely overweight or obese, may already suffer from respiratory problems and/or hyperglycemia, and the use of GH may only exacerbate these problems. Any GH regimen should be closely monitored by a physician.

Bariatric Surgery

Another treatment option that has been presented for those with PWS is bariat-ric surgery. Although bariatric surgery has been sporadically successful as far as short-term reduction in body weight, overall the risks seem to outweigh the benefits in this population. One retrospec-tive review found results ranging from a 2.4% weight loss to a 3.5% weight gain 5 years postsurgery.26 Furthermore, this same study reported a much higher risk of gastric dilation and perforation in those with PWS as opposed to typical obese individuals (27% vs 0.278%), presumably beause of hyperphagia. Many of the typi-cal risks associated with bariatric surgery, such as infection, were observed as well.

It should be known that many indi-viduals with PWS have been successful

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in maintaining a healthy weight without resorting to GH or surgery.21 A combina-tion of diet, exercise, and behavior ther-apy can be very successful in treating the overweight and obesity associated with PWS.

The Interdisciplinary Team

As with so many developmental disabil-ities, no one professional can adequately address all of the issues that come along with PWS. Therefore, working with a team of professionals, preferably who specialize in developmental disabilities, is very strongly recommended.5,22 This team may include a physician, registered dieti-tian, speech and language pathologist, lactation consultant (in infancy), occu-pational and physical therapist, behav-ior therapist, psychologist or psychiatrist, and a social worker. Using health pro-fessionals such as a psychologist or psy-chiatrist can provide support to these families in dealing with the child’s men-tal health, including mood and obsessive-compulsive disorders. Physical therapists, speech language pathologists, occupa-tional therapists, and behavior therapists can help address issues such as strength and movement skills, verbal and articu-lation skills, activities of daily living, and age-appropriate behaviors.

In addition to the various health care professionals, there also must be com-munication between the family, school, and the community. Once the child reaches school age, the implementa-tion of special arrangements and envi-ronmental controls with the school is recommended. This may include mod-ification to the child’s school breakfast and lunch. Parents should work with school personnel to develop an individ-ualized education program (IEP) to meet the individual educational, health, and safety needs of their child.6 The IEP may include alterations to school menus, direct supervision at mealtimes, and supportive services such as counseling. The IEP con-stantly changes and is updated based on the progress and needs of the child. It is common for the members of the medical team, including the nutrition professional, to have input in this document. If special

education is not needed, the child will still need strict dietary guidelines. In this case, a 504 Accommodation Plan, which focuses solely on diet modification, can be used.6 Again, the dietitian should be very involved in this process, especially in helping the parents explain to the school staff the importance of these restrictions. Finally, adaptive physical education should be discussed with the school fac-ulty so that the child is able to participate.

Impact on the Family

Any family with a child who has a developmental disability will, at times, struggle. Having a child with PWS is no exception, especially immediately fol-lowing the birth of the child and dur-ing adolescence.21 Parents have reported marital tension of varying degrees related to depression and the uncertainty of the child’s future, among other things. A wide range of sibling issues have also been reported such as jealousy from the child with PWS that his or her siblings are able to eat freely and extreme over-protectiveness from the non-PWS-affected sibling. Tensions within the community are not uncommon, oftentimes related to temper tantrums and stealing by the child with PWS and also name-calling by children within the community. A psy-chologist should meet with not just the individual with PWS but with the entire family to work through any difficult issues that will inevitably arise.

Last, the financial and time commitment on the part of the caregiver(s) cannot be overlooked. Maintaining regular appoint-ments with each of the team members as recommended can place a great burden on the individual looking after the child, even into adolescence and adulthood. However, the use of an interdisciplinary team approach that combines appoint-ments with multiple health care profes-sionals may minimize the time as well as financial burden of treating this disease.

Although having a child with a devel-opmental disability can cause despair, these families should not expect to live a life of grief. Managing PWS is certainly difficult but can be rewarding with the proper support and guidance.

Expectations in Adulthood

Although the life expectancy of those with PWS is perhaps shorter than that for typical children, individuals with this dis-ease can have a normal life expectancy if weight is controlled.5 In a study of 315 individuals with PWS, Wollmann et al27 found an average body mass index (BMI) of 35 for both males and females, indicat-ing a high prevalence of obesity among adults with PWS. Deaths are most often related to complications from obesity, such as cardiorespiratory failure, apnea, or skin infection, and can occur as young as the teenage years.1 Nutrition profes-sionals should be particularly aware of other causes of death related to eating such as choking due to fast consump-tion of food or gastric rupture from over-eating. These incidents cause 8% and 2% of deaths in the PWS population, respectively.1

Adults with PWS should continue to work with their interdisciplinary team into adulthood to maintain as much con-trol over the disease as possible.1 In gen-eral, individuals with PWS do not ever become socially mature adults and are rarely able to function completely inde-pendently.5 However, residential housing options available for people with PWS and other development disabilities pro-vide some independence for both the patients and their family while still pro-viding the care and support needed on a day-to-day basis.

Conclusion

Prader-Willi syndrome is an extremely complex, multidimensional disease. Although proper nutrition is certainly not the only concern for these families, it may be the most critical as it is cur-rently one of the only treatment options. Nutrition intervention is the only way to prevent death due to severe obesity and its complications and is therefore cru-cial in the management of this disease. Although efforts to find a true cure for the disease are continuing, it is extremely important that nutrition professionals understand how to manage PWS and are armed with strategies that are helpful to

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these families. It is an enormous respon-sibility but also a wonderful challenge for nutrition professionals to know that they truly can help make the difference between life—quality of life—and death for children with PWS and their families.

References

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2. Glenn CC, Deng G, Michaelis RC, et al. DNA methylation analysis with respect to prenatal diagnosis of Angelman and Prader-Willi syndromes and imprinting. Prenat Diagn. 2000;20:300-306.

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4. Bekx MT, Carrel AL, Shriver TC, Li Z, Allen DB. Decreased energy expenditure is caused by abnormal body composition in infants with Prader-Willi syndrome. J Pediatr. 2003;143:372-376.

5. Greenswag LR, Alexander RC, eds. Management of Prader-Willi Syndrome. New York: Springer-Verlag; 1995.

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7. Isaacs JS, Zand DJ. Single-gene auto-somal recessive disorders and Prader-Willi syndrome: an update for food and nutrition professionals. J Am Diet Assoc. 2007;107:466-478.

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9. Cummings DE, Clement K, Purnell JQ, et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med. 2004; 8:643-644.

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children and adolescents with Prader-Willi syndrome. Int J Obes. 2000;24:429-434.

18. Holm VA, Pipes PL. Food and children with Prader-Willi syndrome. Am J Dis Child. 1976;130:1063-1067.

19. Ekvall S, ed. Pediatric Nutrition in Chronic Diseases and Developmental Disorders: Prevention, Assessment, and Treatment. New York: Oxford University Press; 1993.

20. Goldberg DL, Garrett CL, Van Riper C, Warzak WJ. Coping with Prader-Willi syn-drome. J Am Diet Assoc. 2002;102:537-542.

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22. Position of the American Dietetic Association: nutrition in comprehensive program plan-ning for persons with developmental disa-bilities. J Am Diet Assoc. 1997;97:189-193.

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