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 8.1. cm/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 ± 2.1. cm/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.
Bibliographical noteFunding Information:
The authors would like to thank all the study participants and their parents, as well as the study coordinator Jane Kennedy, RN. Research reported in this publication was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) under Award Number K23AR057789 , the National Institutes of Neurological Disorders and Stroke (NINDS)/Diabetes and Digestive and Kidney (NIDDK) of the NIH under Award Number U54NS065768 , a grant from the University of Minnesota Pediatric Foundation , and by the National Center for Advancing Translational Sciences of the NIH Award Number UL1TR000114 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
LEP has previously received research funding (drug only) from Genentech and has provided consulting support to and received grant support from Genzyme . BSM is a consultant for ENDO Pharmaceuticals, Genentech, Ipsen, Novo Nordisk and Sandoz and receives grant/research support from ENDO Pharmaceuticals , Eli Lilly , Ipsen , Novo Nordisk and Sandoz . CBW has been a consultant and recipient of grants from Actelion , Amicus , BioMarin , Genzyme, Shire , and Synageva. WT and PO have no conflicts of interest.
- Body composition
- Growth hormone
- Hunter syndrome
- Hurler syndrome