The Morquio A Clinical Assessment Program: Baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects

• Published in: Molecular genetics and metabolism 2013-05, Vol.109 (1), p.54-61
• Main Authors: Harmatz, Paul, Mengel, Karl Eugen, Giugliani, Roberto, Valayannopoulos, Vassili, Lin, Shuan-Pei, Parini, Rossella, Guffon, Nathalie, Burton, Barbara K., Hendriksz, Christian J., Mitchell, John, Martins, Ana, Jones, Simon, Guelbert, Norberto, Vellodi, Ashok, Hollak, Carla, Slasor, Peter, Decker, Celeste
• Format: Article
• Language: English
• Subjects: Activities of Daily Living; Adolescent; Adult; Child; Child, Preschool; Cross-Sectional Studies; Endurance; Exercise; Female; GALNS; Glycosaminoglycans - metabolism; Humans; Infant; Infant, Newborn; Keratan Sulfate - urine; Lysosomal storage disorder; Male; Morquio; Motor Activity; MPS; Mucopolysaccharidosis IV - diagnosis; Mucopolysaccharidosis IV - epidemiology; Mucopolysaccharidosis IV - genetics; Mucopolysaccharidosis IV - physiopathology; Mucopolysaccharidosis IV - urine; Physical Endurance; Quality of Life; Respiratory function; Respiratory Function Tests; Surveys and Questionnaires; United States
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2013.01.021

The objectives of this study are to quantify endurance and respiratory function and better characterize spectrum of symptoms and biochemical abnormalities in mucopolysaccharidosis IVA subjects. MorCAP was a multicenter, multinational, cross sectional study amended to be longitudinal in 2011. Each study visit required collection of medical history, clinical assessments, and keratan sulfate (KS) levels. Data from the first visit of 325 subjects (53% female) were available. Mean age was 14.5years. Mean±SD height z-scores were −5.6±3.1 as determined by the CDC growth charts. Mean±SD from the 6-minute-walk-test was 212.6±152.2m, revealing limitations in functional endurance testing, and 30.0±24.0stairs/min for the 3-minute-stair-climb test. Respiratory function showed limitations comparable to MPS VI patients; mean±SD was 1.2±0.9l based on forced vital capacity and 34.8±25.5l/min based on maximum voluntary ventilation. Mean urinary keratan sulfate (uKS) was elevated for all ages, and negatively correlated with age. Higher uKS correlated with greater clinical impairment based on height z-scores, endurance and respiratory function tests. The MPS Health Assessment Questionnaire reveals impairments in mobility and activities of daily living in comparison to an age-matched control population. MPS IVA is a multisystem disorder with a continuum of clinical presentation. All affected individuals experience significant functional limitations and reduced quality of life. Older patients have more severe exercise and respiratory capacity limitations, and more frequent cardiac pathology illustrating the progressive nature of disease. ► MorCAP is the first natural history study with quantitative assessments of MPS IVA. ► Endurance, mobility, respiratory function, stature and quality of life are impacted. ► All affected individuals experience significant functional limitations. ► Increasing severity with age illustrates the progressive nature of Morquio A.