6533b7d4fe1ef96bd1262079

RESEARCH PRODUCT

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

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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 (PVC) and maximum voluntary ventilation (MW). 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 PVC and MW were 2.44 +/- 0.68% and 1.01 +/- 2.38%, respectively. PVC and MW 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 PVC and MW showing increase in younger patients, but decrease in older patients, are likely to be influenced by growth. Changes in 6MVVT may represent a sensitive measure of disease progression in ambulatory Morquio A patients. (C) 2014 BioMarin Pharmaceutical Inc. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). UCSF Benioff Childrens Hosp Oakland, Oakland, CA USA MC Univ Mainz, Ctr Pediat & Adolescent Med, Mainz, Germany Dept Genet UFRGS, Med Genet Serv HCPA, Porto Alegre, RS, Brazil INAGEMP, Porto Alegre, RS, Brazil Hop Univ Necker Enfants Malad, Inst IMAGINE, Reference Ctr Inherited Metab Dis, Paris, France Mackay Mem Hosp, Taipei, Taiwan Mackay Med Coll, Taipei, Taiwan San Gerardo Univ Hosp, Dept Pediat, Rare Metab Dis Unit, Monza, Italy Hop Femme Mere Enfant, Lyon, France Ann & Robert H Lurie Childrens Hosp, Chicago, IL USA Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA Birmingham Childrens Hosp NHS Fdn Trust, Birmingham, W Midlands, England McGill Univ, Ctr Hlth, Montreal, PQ, Canada Universidade Federal de São Paulo, São Paulo, Brazil Univ Manchester, CMFT, Manchester Ctr Genom Med, Manchester, Lancs, England Hosp Ninos Cordoba, Cordoba, Argentina Great Ormond St Hosp Children NHS Fdn Trust, London, England Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands BioMarin Pharmaceut Inc, Novato, CA USA Universidade Federal de São Paulo, EPM, São Paulo, Brazil Web of Science