Effect of enzyme replacement therapy on growth in patients with Hunter syndrome: results from the Hunter Outcome Survey. M. Beck¹, J. Muenzer², M. Scarpa³, G. Schulze Frenking¹, E. Wraith⁴ on behalf of the HOS investigators 1) Pediatric Dept, Univ Mainz, Mainz, Germany; 2) Pediatric Dept, Univ North Carolina, USA; 3) Pediatric Dept, Univ Padova, Padova, Italy; 4) Willink Biochemical Genetics Unit, Royal Manchester Children's Hosp, Manchester, UK.

   Introduction: The Hunter Outcome Survey (HOS) is a global database covering the natural history of Hunter syndrome (MPS II) and the safety and effectiveness of enzyme replacement therapy (ERT) with idursulfase (ElapraseTM; Shire HGT). Untreated patients with MPS II have markedly reduced growth after 5-8y of age. The first data on the effects of ERT on the growth of patients with MPS II are provided here. Methods: On 15 May 2008, there were 421 prospective patients in HOS (i.e. alive when enrolled); 221 were receiving ERT. This analysis included all patients with available height data 1y before and 1y after ERT. Results: Height data were available for 29 patients; 2 were excluded because they were aged 20y at the start of ERT (baseline). Of the 27 eligible patients, 17 were aged 12y (3-11) and 10 were aged 12y (12-18) at baseline. Mean (SD) changes in height were: 2.9 (2.3) cm before and 4.7 (3.0) cm after ERT for patients aged 12y; 1.8 (2.3) cm before and 3.2 (2.7) cm after ERT for patients aged 12y; and 2.5 (2.3) cm before and 4.1 (2.9) cm after ERT for all patients. Mean (SD) change in height velocity 1y before to 1y after ERT was +1.6 (3.1) cm/y, and mean changes in z-scores were -0.5 (0.3) before and -0.1 (0.5) after ERT. Changes were more notable in patients aged 12y at baseline. Mean (SD) changes in height velocity for patients 12y and 12y were +1.8 (3.4) and +1.4 (2.5) cm/y, respectively. Mean changes in z-scores for patients 12y before and after ERT were -0.4 (0.2) and 0.0 (0.4), respectively, and for patients 12y were -0.5 (0.5) and -0.3 (0.5), respectively. Conclusions: In a non-age-stratified analysis of outcome survey data, we observed an acceleration of growth in patients with MPS II given ERT with idursulfase for 1y. Ongoing collection of data in HOS, including analysis of ERT and pubertal development status (Tanner stage), will further elucidate the effect of idursulfase ERT on growth.