TY - JOUR
T1 - Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome
AU - Harmatz, Paul R.
AU - Mengel, Karl Eugen
AU - Giugliani, Roberto
AU - Valayannopoulos, Vassili
AU - Lin, Shuan Pei
AU - Parini, Rossella
AU - Guffon, Nathalie
AU - Burton, Barbara K.
AU - Hendriksz, Christian J.
AU - Mitchell, John J.
AU - Martins, Ana Maria
AU - Jones, Simon A.
AU - Guelbert, Norberto
AU - Vellodi, Ashok
AU - Wijburg, Frits A.
AU - Yang, Ke
AU - Slasor, Peter
AU - Decker, Celeste
N1 - Funding Information:
P. R. Harmatz has provided consulting services, received research grants, participated in advisory board meetings and received speaker honoraria and travel support from BioMarin Pharmaceutical Inc. (BioMarin). K. Yang, P. Slasor and C. Decker are employees and stockholders of BioMarin. All other authors are investigators and/or consultants of BioMarin, have received research grants from BioMarin, and have received travel support from BioMarin.
Funding Information:
The authors would like to acknowledge the patients and families who participated in this investigation and all MorCAP investigators and clinic coordinators. This study was supported, in part, with funds provided by the National Center for Research Resources , 5M01 RR-01271 (Dr. Harmatz). The authors wish to thank Adrian Quartel, Elaina Jurecki, Ken Martin, Tom Lester and Renée Shediac of BioMarin Pharmaceutical Inc. for their assistance in the preparation of this manuscript.
Publisher Copyright:
© 2014.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Objectives: Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al., Mol Genet Metab, 2013). Here, 1- and 2-year longitudinal endurance and respiratory function data are presented. Methods: Endurance was assessed using the 6-minute walk test (6MWT) and the 3-minute stair climb test (3MSCT). Respiratory function was evaluated by measuring forced vital capacity (FVC) and maximum voluntary ventilation (MVV). Data were analyzed using repeated measures ANCOVA models. Annualized estimates of change were determined using model estimates and interpolation. Results: 353, 184, and 78 subjects were assessed at Year 0 (baseline), Year 1, and Year 2, respectively. The overall annualized estimate of change (SE) in 6MWT distance was - 4.86 ± 3.25. m; a larger decline of - 6.84 ± 5.38. m was observed in the subset of subjects meeting the inclusion/exclusion criteria of the Phase 3 clinical trial of elosulfase alfa (≥. 5. years of age with baseline 6MWT distance ≥. 30 and ≤. 325. m). In contrast, little change (- 0.14 ± 0.60. stairs/min) was observed in 3MSCT. Annualized changes (SE) in FVC and MVV were 2.44 ± 0.68% and 1.01 ± 2.38%, respectively. FVC and MVV increased in patients aged ≤. 14. years, but decreased in older patients. Conclusions: The natural history of Morquio A syndrome is characterized by progressive impairment of endurance as measured by the 6MWT. Longitudinal trends in FVC and MVV showing increase in younger patients, but decrease in older patients, are likely to be influenced by growth. Changes in 6MWT may represent a sensitive measure of disease progression in ambulatory Morquio A patients.
AB - Objectives: Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al., Mol Genet Metab, 2013). Here, 1- and 2-year longitudinal endurance and respiratory function data are presented. Methods: Endurance was assessed using the 6-minute walk test (6MWT) and the 3-minute stair climb test (3MSCT). Respiratory function was evaluated by measuring forced vital capacity (FVC) and maximum voluntary ventilation (MVV). Data were analyzed using repeated measures ANCOVA models. Annualized estimates of change were determined using model estimates and interpolation. Results: 353, 184, and 78 subjects were assessed at Year 0 (baseline), Year 1, and Year 2, respectively. The overall annualized estimate of change (SE) in 6MWT distance was - 4.86 ± 3.25. m; a larger decline of - 6.84 ± 5.38. m was observed in the subset of subjects meeting the inclusion/exclusion criteria of the Phase 3 clinical trial of elosulfase alfa (≥. 5. years of age with baseline 6MWT distance ≥. 30 and ≤. 325. m). In contrast, little change (- 0.14 ± 0.60. stairs/min) was observed in 3MSCT. Annualized changes (SE) in FVC and MVV were 2.44 ± 0.68% and 1.01 ± 2.38%, respectively. FVC and MVV increased in patients aged ≤. 14. years, but decreased in older patients. Conclusions: The natural history of Morquio A syndrome is characterized by progressive impairment of endurance as measured by the 6MWT. Longitudinal trends in FVC and MVV showing increase in younger patients, but decrease in older patients, are likely to be influenced by growth. Changes in 6MWT may represent a sensitive measure of disease progression in ambulatory Morquio A patients.
KW - 6minute walk test
KW - Endurance
KW - Longitudinal analysis
KW - MPS IVA
KW - Morquio A
KW - Mucopolysaccharidosis IVA
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U2 - 10.1016/j.ymgme.2014.10.015
DO - 10.1016/j.ymgme.2014.10.015
M3 - Article
C2 - 25582974
AN - SCOPUS:84921759170
VL - 114
SP - 186
EP - 194
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
SN - 1096-7192
IS - 2
ER -
