title: Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome.
abstract: OBJECTIVE
  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±3.25m; a larger decline of -6.84±5.38m was observed in the subset of subjects meeting the inclusion/exclusion criteria of the Phase 3 clinical trial of elosulfase alfa (≥5years of age with baseline 6MWT distance ≥30 and ≤325m). In contrast, little change (-0.14±0.60stairs/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 ≤14years, 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.
authors.affiliation: UCSF Benioff Children's Hospital Oakland, Oakland, CA, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Harmatz
authors.affiliation: Villa Metabolica, Centre for Pediatric and Adolescent Medicine, MC University of Mainz, Mainz, Germany.
authors.forename: Karl Eugen
authors.initials: KE
authors.lastname: Mengel
authors.affiliation: Medical Genetics Service/HCPA, Department of Genetics/UFRGS and INAGEMP, Porto Alegre, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.affiliation: Reference Center for Inherited Metabolic Disease, Institut IMAGINE, Hôpital Universitaire Necker-Enfants Malades, Paris, France.
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.affiliation: Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
authors.forename: Shuan-Pei
authors.initials: SP
authors.lastname: Lin
authors.affiliation: Rare Metabolic Diseases Unit, Department of Pediatrics, San Gerardo University Hospital, Monza, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.affiliation: Hôpital Femme Mère Enfant, Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.affiliation: Ann and Robert H. Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Burton
authors.affiliation: Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Hendriksz
authors.affiliation: McGill University Health Centre, Montreal, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Mitchell
authors.affiliation: Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
authors.affiliation: Manchester Centre for Genomic Medicine, CMFT, University of Manchester, Manchester, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Hospital de Niños de Cordoba, Cordoba, Argentina.
authors.forename: Norberto
authors.initials: N
authors.lastname: Guelbert
authors.affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Ashok
authors.initials: A
authors.lastname: Vellodi
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Frits A
authors.initials: FA
authors.lastname: Wijburg
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Slasor
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, CA, USA. Electronic address: cdecker@bmrn.com.
authors.forename: Celeste
authors.initials: C
authors.lastname: Decker
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D008451:Maximal Voluntary Ventilation; D008875:Middle Aged; D009043:Motor Activity; D009085:Mucopolysaccharidosis IV / Q000503:physiopathology*; D010807:Physical Endurance; D012119:Respiration; D055815:Young Adult
keywords: 6minute walk test; Endurance; Longitudinal analysis; MPS IVA; Morquio A; Mucopolysaccharidosis IVA