Our long-term goal is to identify and test new therapies for musculoskeletal disease in MPS. The objective of this proposed longitudinal observational study is to document the progression of skeletal disease and identify biomarkers that either predict disease severity or could be used as therapeutic targets in individuals with MPS I, II, and VI. The rationale for this project is to obtain baseline data for future therapeutic clinical trials and to identify potential therapeutic targets. Our central hypothesis is that skeletal disease will progress over time and that biomarkers of inflammation, and bone and cartilage turnover, will predict the severity of skeletal disease over time. Therefore, this study has the following specific aims (SA):