Abstract
Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism.
The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients.
The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.
Prader-Willi syndrome (PWS) is a variable and complex genetic neurobehavioral disorder resulting from abnormality on the 15th chromosome. It occurs in males and females equally. Prevalence estimates range from 1:15,000 to 1:25,000.
PWS typically causes low muscle tone, short stature if not treated with growth hormone, cognitive deficits, incomplete Makinglove development, problem behaviours, and excessive, uncontrolled feeling of hunger which, coupled with a metabolism that utilizes drastically fewer calories than normal, can lead to excessive eating and life-threatening obesity
Infants with PWS may require the use of feeding tubes to obtain adequate nutrition. Children with PWS are prone to developing abnormal curvature of spine called scoliosis which can be treated with bracing, casting or surgery. Vision problems in PWS can be treated with corrective lenses or surgery. Many people with PWS have sensory integration deficits and benefit from sensory integration programs. They have decreased pain signals which masks injuries and illnesses. Individuals with PWS have anxiety, obsessive compulsive behaviour, temper outbursts lack of impulse control that can be managed with therapies and medications.
Early diagnosis and optimal clinical care can improve outcomes for people with PWS, and one proven intervention is growth hormone therapy. In PWS, growth hormone is effective not only in increasing height, but also in:
- Decreasing body fat
- Increasing muscle mass
- Improving weight distribution
- Increasing stamina and physical performance
- Improving bone health
- Positive effects on cognition, behaviour and quality of life
- Improved respiratory function
- Improved head circumference
Growth Hormone therapy, started in infants, as early as 3 months of age, significantly changes the natural history of PWS in a beneficial and clinically meaningful way.
GH therapy is able to ameliorate the phenotypic appearance of the syndrome, as well as to improve body composition, physical strength, and cognitive level. In this regard, however, some pathophysiologic and clinical questions still remain, representing a challenge to give the most appropriate care to PWS patients.
Benefits of Growth Hormone Therapy for PWS
Human growth hormone is effective not only in increasing height, but also in decreasing body fat, increasing muscle mass, improving weight distribution, increasing stamina, and increasing bone mineral density in PWS. In addition to these positive effects on growth and body composition, studies suggest positive effects on development and behavior.
There is increasing evidence that HGH treatment may improve cognitive performance in children with PWS. A study in 2016 by Dykens and colleagues [Cognitive and adaptive advantages of growth hormone treatment in children with Prader-Willi syndrome] showed that children with PWS who received HGH had higher IQ scores and better communication and daily living skills than children who had not received HGH. As with other studies, the results from the Dykens study suggest that "earlier is better": children starting HGH before 12 months of age had higher IQ scores compared to children who started HGH at ages 1–5.
Although the level of HGH normally decreases as people reach their final adult height, HGH is still produced in normal adults, and is thought to be important for maintaining good body compostion and cognitive performance. There is mounting evidence that adults with PWS benefit from continued HGH therapy, even after growth is completed. Adults treated with growth hormone show improvement in body composition, mental speed, mental flexibility, and motor performance (see studies here, here and here).
Research Shows Positive Results and a Good Safety Profile
The research on HGH therapy supports its benefits when used for PWS treatment, while continuing the trend of a reassuring safety profile. One concern when GH first came into clinical use was whether its in children might increase the risk of leukemia. But the study Long-term safety of recombinant human growth hormone in children [Bell, 2010] followed almost 50,000 children who received growth hormone between 1985 and 2006 (some with PWS, some on HGH for other reasons) and does not support that concern: slightly less than the expected number of children in this group developed leukemia (3 cases observed, 5.6 expected).
Other concerns specific for PWS include scoliosis and breathing issues. Scoliosis is very common in PWS, and some physicians may be concerned about HGH use in individuals with PWS who develop scoliosis. But the data suggests that HGH does not worsen scoliosis outcomes; if anything, it is associated with better outcomes, perhaps due to strengthened muscles (see guidelines, below, as well as a recent review and a previous FPWR blog). Finally, HGH may cause tonsils to grow, which can worsen obstructive sleep apnea, and thus a sleep study is recommended before and shortly after starting HGH, with involvement of an ears, nose and throat doctor to address enlarged tonsils, as needed.
You must be logged in to post a comment.