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Growth Hormone Therapy Improves Mental and Motor Development in Young Prader-Willi Patients« Back to Volume 24, Issue 2, November 2008 - Table of Contents Prader-Willi syndrome (PWS) is increasingly diagnosed in early infancy because pediatricians and neonatologists are more aware of the clinical picture (muscular hypotonia, feeding difficulties, failure to thrive, and psychomotor delay). The genetic cause of PWS is an alteration in the long arm of paternal chromosome 15 (by deletion, microdeletion, maternal uniparental disomy, mutation of imprinting centre, chromosomal rearrangement). It is well known that methylation analysis is an efficient tool for early and reliable diagnosis of PWS. Children with PWS have an abnormal body composition with a relatively high body fat percentage and a low lean body mass (LBM). Even in PWS infants who are underweight, body fat percentage is high. Treatment with human growth hormone (hGH) in older children with PWS results not only in an increased growth response but also in an improvement in body composition, with a decline in fat percentage and an increment in LBM, resulting in increased muscle strength and agility. The effects of hGH therapy on psychosocial development in PWS have not been well studied. Festen and colleagues evaluated psychomotor development in PWS infants and toddlers during hGH treatment compared to controls. Forty-three PWS infants were evaluated at baseline; 29 of them were randomized into a GH group (n=15) receiving 1 mg/m2/day of GH or a non-GH-treated control group (n= 14). At baseline, and after 12 months of GH treatment, an analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age, and changes during follow-up were calculated. Infants in the GH group had a median age of 2.3 years (interquartile range [IQR] 1.7–3.0) and the median age of the control group was 1.5 years (IQR 1.2–2.7) (p=0.17). Both mental and motor development improved significantly during the first year of study in the GH group vs the control group: median (IQR) change was +9·3% (–5.3 to 13.3) vs –2.9% (–8.1 to 4.9) (p<0.05) in mental development and +11.2% (–4.9 to 22.5) vs –18.5% (–27.9 to 1.8) (p< 0.05) in motor development, respectively. Thus, one year of hGH treatment significantly improved mental and motor development in PWS infants compared to controls. Infants with lower developmental age had the greatest improvement in motor development. There was also a normalization of head circumference and a significant increase in height SDS in the GH group, but not in the control group after one year of hGH treatment. The hGH was well tolerated; compared to randomized controls, hGH did not induce disadvantageous effects on sleep-related breathing disorders, carbohydrate metabolism and thyroid hormone levels. Editor’s CommentThe best point of time to initiate hGH therapy for PWS remains unknown. Eiholzer et al1 do not recommend starting hGH therapy in PWS in the first year of life because of an increased risk of sudden infant death during this period. Festen and colleagues evaluated whether hGH treatment started at an early age could contribute to an improvement in mental and motor development in a group of PWS patients. They found a significant improvement of both mental and motor development in the GH group compared to the control group. Children with lower developmental age had the greatest improvement in motor development, suggesting that hGH treatment might be considered at an early developmental age to optimize the hGH effects on motor development. They also found that hGH did not induce disadvantageous effects on sleep-related breathing disorders. In their study, insulin-like growth factor (IGF)-I levels increased rapidly during hGH treatment from below the normal range to the high-normal range. IGF-I receptors have been localized in several areas in the human brain, indicating that IGF-I may have a neuroregulatory role in the central nervous system. Theoretically, IGF-I may directly influence the central nervous system or hGH might induce local IGF-I expression in brain tissue, thereby improving psychomotor development. Another possible explanation for the improvement in mental development during hGH treatment might be that, because of the improved motor development, children are able to sit, stand and walk independently, enabling them to explore and interact with the environment and resulting in a subsequent improvement in mental development. The results of this study suggest that early start with hGH might be beneficial in PWS. However, long-term double-blind studies are needed to evaluate the efficacy and safety of the early treatment with hGH on cognition in childhood and adulthood. Yoshikazu Nishi, MD Reference - (linked to
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Volume 25 Number 1
June 2009
www.GGHjournal.com
ISSN 1932-9032
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