Abstract
A few cases of death worldwide during GH treatment in pediatric patients with Prader-Willi syndrome (PWS) have been recently described. The evaluation of further cases is needed to better identify possible causal mechanism(s), as well as to suggest some additional guidelines for prevention. We report the death of 2 additional children with genetically confirmed PWS in the first months of GH therapy. Case 1: This 3.9-yr-old girl was born at 39 weeks gestation. Low GH response to two stimulation tests was observed. GH administration was started at the age of 3.5 yr (0.33 mg/kg per week), when the patient was at 130% of her ideal body weight (ibw). Hypertrophy of adenoids was previously demonstrated. Snoring and sleep apnea were present before GH treatment, and did not increase during therapy. Four months later she died at home suddenly in the morning. Case 2: This patient was a 6.3-yr-old boy. He was born at term after an uneventful pregnancy. At the age of 6 yr, his weight was at 144% of his ibw. He showed reduced GH secretion during provocation tests, and GH therapy was started (0.20 mg/kg per week). The previously reported nocturnal respiratory impairment had worsened after beginning GH administration. Tonsils and adenoids hypertrophy were noted. At the age of 6.3 yr he died at home in the morning following an acute crisis of apnea. These additional cases seem to confirm that some children with PWS may be at risk of sudden death at the beginning of GH therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cassidy SB. Prader-Willi syndrome. J Med Genet 1997, 34: 917–23.
Burman P, Ritzen EM, Lindgren AC. Endocrine dysfunction in Prader-Willi syndrome: a review with special reference to GH. Endocr Rev 2001, 22: 787–99.
Lee DK, Allen DB, Angulo MA, et al. Consensus Statement — Prader-Willi syndrome: Growth Hormone (GH)/Insulin-Like Growth Factor Axis deficiency and GH treatment. Endocrinologist 2000, 10 (Suppl 1): 71S–74S.
Carrel AL, Myers SE, Whitman BY, Allen DB. Growth hormone improves body composition, fat utilization, physical strenght and agility, and growth in Prader-Willi syndrome: a controlled study. J Pediatr 1999, 134: 215–21.
Haqq AM, Stadler DD, Jackson RH, Rosenfeld RG, Purnell JQ, LaFranchi SH. Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome. J Clin Endocrinol Metab 2003, 88: 2206–12.
Eiholzer U, Malich S, l’Allemand D. Does growth hormone therapy improve motor development in infants with Prader-Willi syndrome? Eur J Pediatr 2000, 150: 299.
Eiholzer U, Nordmann Y, l’Allemand D. Fatal outcome of sleep apnoea in PWS during the initial phase of growth hormone treatment: a case report. Horm Res 2002, 58 (Suppl 3): 24–6.
Nordmann Y, Eiholzer U, l’Allemand D, Mirjanic S, Markwalder C. Sudden death of an infant with Prader-Willi syndrome — Not a unique case? Biol Neonate 2002, 82: 139–41.
Van Vliet G, Deal CL, Crock PA, Robitaille Y, Oligny LL. Sudden death in growth-hormone treated children with Prader-Willi syndrome. J Pediatr 2004, 144: 129–31.
Sacco M, Di Giorgio G. Sudden death in Prader-Willi syndrome during GH therapy. Horm Res 2005, 63: 29–32.
Smith A, Loughnan G, Steinbeck K. Death in adults with Prader-Willi syndrome may be correlated with maternal uniparental disomy. J Med Genet 2003, 40: e63.
Stevenson DA, Anaya TM, Clayton-Smith J, et al. Unexpected death and critical illness in Prader-Willi syndrome: Report of ten individuals. Am J Med Genet A 2004, 124: 158–64.
Whittington JE, Holland AJ, Webb T, Butler J, Clarke D, Boer H. Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet 2001, 38: 792–8.
Schrander-Stumpel CTRM, Curfs LMG, Sastrowijoto P, Cassidy SB, Schrander JJP, Fryns J-P. Prader-Willi syndrome: Causes of death in an international series of 27 cases. Am J Med Genet A 2004, 124: 333–8.
Vogels A, Van Den Ende J, Keymolen K, et al. Minimun prevalence, birth incidence and cause of death for Prader-Willi syndrome in Flanders. Eur J Hum Genet 2004, 12: 238–40.
Oiglane E, Ounap K, Bartsch O, Rein R, Talvik V. Sudden death of a girl with Prader-Willi syndrome. Genetic Counseling 2002, 13: 459–64.
Schluter B, Buschatz D, Trowitzsch E, Aksu F, Andler W. Respiratory control in children with Prader-Willi syndrome. Eur J Pediatr 1997, 156: 65–8.
Hakonarson H, Moskovitz J, Daigle KL, Cassidy SB, Cloutier MM. Pulmonary function abnormalities in Prader-Willi syndrome. J Pediatr 1995, 126: 565–70.
Lindgren AC, Hellstrom LG, Ritzen EM, Milerad J. Growth hormone treatment increases CO2 response, ventilation and central inspiratory drive in children with Prader-Willi syndrome. Eur J Pediatr 1999, 158: 936–40.
l’Allemand D, Eiholzer U, Schlumpf M, Steinert H, Riesen W. Cardiovascular risk factors improve under 3 years of growth hormone therapy in Prader-Willi syndrome. Eur J Pediatr 2000, 159: 835–42.
Zipf WB. Prader-Willi syndrome: the care and treatment of infants, children, and adults. Adv Pediatr 2004, 51: 409–34.
Ahmad MU, Choy YS, Hung LC, et al. Dilated cardiomyopathy in two infants with Prader-Willi syndrome and cytogenetically visible microdeletion of 15q11–q14. Am J Hum Genet 2001, 69: S282 (abstract).
Frustaci A, Gentiloni N, Russo MA. Growth hormone in the treatment of dilated cardiomyopathy. N Engl J Med 1996, 335: 672.
Author information
Authors and Affiliations
Consortia
Corresponding author
Rights and permissions
About this article
Cite this article
Grugni, G., Livieri, C., Corrias, A. et al. Death during GH therapy in children with Prader-Willi syndrome: Description of two new cases. J Endocrinol Invest 28, 554–557 (2005). https://doi.org/10.1007/BF03347245
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347245