title: Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1-2 years in children with Hurler or Hunter syndrome.
abstract: Patients with Hurler or Hunter syndrome typically have moderate to severe growth deficiencies despite therapy with allogeneic hematopoietic stem cell transplantation and/or enzyme replacement therapy. It is unknown whether treatment with recombinant human growth hormone (hGH) can improve growth in these children. The objectives of this study were to determine the effects of hGH on growth, bone mineral density (BMD), and body composition in children with Hurler or Hunter syndrome enrolled in a longitudinal observational study. The difference in annual change in outcomes between hGH treated and untreated subjects was estimated by longitudinal regression models that adjusted for age, Tanner stage, and sex where appropriate. We report on 23 participants who completed at least 2 annual study visits (10 [43%] treated with hGH): Hurler syndrome (n=13) average age of 9.8 ± 3.1 years (range 5.3-13.6 years; 54% female) and Hunter syndrome (n=10) average age of 12.0 ± 2.7 years (range 7.0-17.0 years; 0% female). As a group, children with Hurler or Hunter syndrome treated with hGH had no difference in annual change in height (growth velocity) compared to those untreated with hGH. Growth velocity in hGH treated individuals ranged from -0.4 to 8.1cm/year and from 0.3 to 6.6 cm/year in the untreated individuals. Among children with Hunter syndrome, 100% (N=4) of those treated but only 50% of those untreated with hGH had an annual increase in height standard deviation score (SDS). Of the individuals treated with hGH, those with GHD had a trend towards higher annualized growth velocity compared to those without GHD (6.5 ± 1.9 cm/year vs. 3.5 ± 2.1cm/year; p=.050). Children treated with hGH had greater annual gains in BMD and lean body mass. In conclusion, although as a group we found no significant difference in growth between individuals treated versus not treated with hGH, individual response was highly variable and we are unable to predict who will respond to treatment. Thus, a trial of hGH may be appropriate in children with Hurler or Hunter syndrome, severe short stature, and growth failure. However, efficacy of hGH therapy should be evaluated after 1 year and discontinued if there is no increase in growth velocity or height SDS. Finally, the long-term benefits of changes in body composition with hGH treatment in this population are unknown.
authors.affiliation: University of Minnesota, Department of Pediatrics, Minneapolis, MN, USA. Electronic address: polgr001@umn.edu.
authors.forename: Lynda E
authors.initials: LE
authors.lastname: Polgreen
authors.affiliation: University of Minnesota, School of Public Health, Division of Biostatistics, Minneapolis, MN, USA. Electronic address: thoma003@umn.edu.
authors.forename: William
authors.initials: W
authors.lastname: Thomas
authors.affiliation: University of Minnesota, Department of Pediatrics, Minneapolis, MN, USA. Electronic address: orcha001@umn.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: University of Minnesota, Department of Pediatrics, Minneapolis, MN, USA. Electronic address: whitley@umn.edu.
authors.forename: Chester B
authors.initials: CB
authors.lastname: Whitley
authors.affiliation: University of Minnesota, Department of Pediatrics, Minneapolis, MN, USA. Electronic address: mille685@umn.edu.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D001823:Body Composition / Q000187:drug effects*; D001827:Body Height / Q000187:drug effects*; D015519:Bone Density / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D007066:Iduronate Sulfatase / Q000378:metabolism; D007068:Iduronidase / Q000172:deficiency; D008137:Longitudinal Studies; D008297:Male; D008059:Mucopolysaccharidosis I / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007066:Iduronate Sulfatase; D007068:Iduronidase
keywords: BMD; BMI; Body composition; CSF; ERT; GAG; GHD; Growth; Growth hormone; HCT; Hunter syndrome; Hurler syndrome; IH; LBM; MPS; Mucopolysaccharidosis; SCFE; SDS; SGA; TBI; body mass index; bone mineral density; central spinal fluid; enzyme replacement therapy; glycosaminoglycan; growth hormone deficiency; hGH; hematopoietic stem cell transplantation; intracranial hypertension; lean body mass; mucopolysaccharidosis; recombinant human growth hormone; slipped capital femoral epiphysis; small for gestational age; standard deviation score; total body irradiation