title: Threshold effect of urinary glycosaminoglycans and the walk test as indicators of disease progression in a survey of subjects with Mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).
abstract: A cross-sectional survey in individuals affected with the lysosomal storage disease Mucopolysaccharidosis VI (MPS VI) was conducted to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of the disease. The survey evaluated 121 bona fide MPS VI-affected individuals over the age of 4 years from 15 countries across the Americas, Europe, and Australasia representing greater than 10% of the estimated world prevalence of the disease. A medical history, complete physical exam, urinary GAG determination, and assessment of several clinical measures related to physical endurance, pulmonary function, joint range of motion, strength, and quality of life were completed for each participant. Although a wide variation in clinical presentation was observed, several general findings were obtained reflecting progression of the disease. Impaired physical endurance, as measured by the distance achieved in a 6-min walk, could be demonstrated across all age groups of MPS VI-affected individuals. High urinary GAG values (>200 mug/mg creatinine) were associated with an accelerated clinical course comprised of age-adjusted short stature and low body weight, impaired endurance, compromised pulmonary function, and reduced joint range of motion. An unexpected result was the predominance of urinary GAG values <100 mug/mg creatinine for those participants over the age of 20 years. Pending the collection of longitudinal data, these results suggest that urinary GAG levels predict clinical morbidity, and longer-term survival is associated with urinary GAG levels below a threshold of 100 mug/mg creatinine.
authors.affiliation: BioMarin Pharmaceutical Inc., Novato, California, USA. sswiedler@BMRN.com
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Swiedler
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.forename: Manal
authors.initials: M
authors.lastname: Bajbouj
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Ida
authors.initials: I
authors.lastname: Schwartz
authors.forename: Paul
authors.initials: P
authors.lastname: Harmatz
authors.forename: James E
authors.initials: JE
authors.lastname: Wraith
authors.forename: Jane
authors.initials: J
authors.lastname: Roberts
authors.forename: David
authors.initials: D
authors.lastname: Ketteridge
authors.forename: John J
authors.initials: JJ
authors.lastname: Hopwood
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon
authors.forename: M Clara
authors.initials: MC
authors.lastname: Sá Miranda
authors.forename: Elisa Leão
authors.initials: EL
authors.lastname: Teles
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
authors.forename: Cheri
authors.initials: C
authors.lastname: Piscia-Nichols
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003627:Data Interpretation, Statistical; D018450:Disease Progression; D005260:Female; D006025:Glycosaminoglycans / Q000652:urine*; D006306:Health Surveys; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D009087:Mucopolysaccharidosis VI / Q000473:pathology* / Q000503:physiopathology / Q000652:urine; D011788:Quality of Life; D016059:Range of Motion, Articular; D012129:Respiratory Function Tests; D011795:Surveys and Questionnaires; D014792:Visual Acuity; D016138:Walking / Q000502:physiology*
chemical_list: D006025:Glycosaminoglycans