J Clin Endocrinol Metab. 2010 Jan 8;
Authors: Carrel AL, Myers SE, Whitman BY, Eickhoff J, Allen DB
Background: Children with Prader-Willi syndrome (PWS) have decreased muscle mass, hypotonia, and impaired linear growth. Recombinant human GH (hGH) treatment reportedly improves body composition and physical function in children with PWS, but these studies lack long-term control data. To assess the impact of hGH therapy begun early in life on the natural history of PWS, we compared height, body composition, and strength in similar-age children with PWS naïve to hGH with those treated with hGH for 6 yr.
Objectives: Forty-eight children with PWS were studied: 21 subjects (aged 6-9 yr) treated with hGH for 6 yr (beginning at 4-32 months, mean 13 +/- 6 months) were compared with 27 children of similar age (5-9 yr) prior to treatment with hGH. Percent body fat, lean body mass, carbohydrate/lipid metabolism, and motor strength were compared using analysis of covariance.
Results: PWS children treated with hGH demonstrated lower body fat (mean, 36.1 +/- 2.1 vs. 44.6 +/- 1.8%, P < 0.01), greater height (131 +/- 2 vs. 114 +/- 2 cm; P < 0.001), greater motor strength [increased standing broad jump 22.9 +/- 2.1 vs. 14.6 +/- 1.9 in. (P < 0.001) and sit-ups 12.4 +/- 0.9 vs. 7.1 +/- 0.7 in 30 sec (P < 0.001)], increased high-density lipoprotein cholesterol (58.9 +/- 2.6 vs. 44.9 +/- 2.3 mg/dl, P < 0.001), decreased low-density lipoprotein (100 +/- 8 vs. 131 +/- 7 mg/dl, P < 0.01), and no difference in fasting glucose or insulin.
Conclusions: hGH treatment in children with PWS, begun prior to 2 yr of age, improves body composition, motor function, height, and lipid profiles. The magnitude of these effects suggests that long-term hGH therapy favorably alters the natural history of PWS to an extent that exceeds risks and justifies consideration for initiation during infancy.
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From the Prader-Willi Syndrome Association – USA (http://www.pwsausa.org):
What is Prader-Willi Syndrome?
A disorder of chromosome 15
Prevalence: 1:12,000- 15,000 (both sexes, all races)
Major characteristics: hypotonia, hypogonadism, hyperphagia, cognitive impairment, difficult behaviors
Major medical concern: morbid obesity
Prader-Willi syndrome (PWS) is the most common known genetic cause of life-threatening obesity in children. Although the cause is complex it results from an abnormality on the 15th chromosome. It occurs in males and females equally and in all races. Prevalence estimates have ranged from 1:8,000 to 1:25,000 with the most likely figure being 1:15,000.
PWS typically causes low muscle tone, short stature if not treated with growth hormone, incomplete sexual development, and a chronic feeling of hunger that, coupled with a metabolism that utilizes drastically fewer calories than normal, can lead to excessive eating and life-threatening obesity. The food compulsion makes constant supervision necessary. Average IQ is 70, but even those with normal IQs almost all have learning issues. Social and motor deficits also exist. At birth the infant typically has low birth weight for gestation, hypotonia (weak muscles), and difficulty sucking due to the hypotonia which can lead to a diagnosis of failure to thrive. The second stage (“thriving too well”), has a typical onset between the ages of two and five, but can be later. The hyperphagia (extreme unsatisfied drive to consume food) lasts throughout the lifetime. Children with PWS have sweet and loving personalities, but this phase is also characterized by increased appetite, weight control issues, and motor development delays along with some behavior problems and unique medical issues.