Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome

Paul R. Harmatz, Karl Eugen Mengel, Roberto Giugliani, Vassili Valayannopoulos, Shuan Pei Lin, Rossella Parini, Nathalie Guffon, Barbara K. Burton, Christian J. Hendriksz, John J. Mitchell, Ana Maria Martins, Simon A. Jones, Norberto Guelbert, Ashok Vellodi, Frits A. Wijburg, Ke Yang, Peter Slasor, Celeste Decker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)186-194
Number of pages9
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - Feb 1 2015


  • 6minute walk test
  • Endurance
  • Longitudinal analysis
  • Morquio A
  • Mucopolysaccharidosis IVA

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Molecular Biology
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism


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