Individuals with MPS I/MPS II have elevated GAG levels in urine, compared with age-matched non-affected individuals.1,2 Therefore, measurement of urinary GAG (UGAG) concentration is used as a screening test when there is clinical suspicion of MPS I/MPS II.3

The UGAG assay detects the type of GAG present.2 Because the different enzyme deficiencies in MPS I and MPS II affect the same GAGs, dermatan sulfate and heparan sulphate, a finding of higher than normal concentrations of these GAGs in the urine is not diagnostic of the specific type of MPS.3 Urinary GAG concentrations are not a reliable indicator of disease severity.4,5

When the UGAG result is positive, an enzyme assay needs to be performed to confirm diagnosis and to identify the type of MPS. A negative UGAG result does not rule out diagnosis of MPS as false-negative results may occur. This is due to insufficient sensitivity of the assay and urine samples that are too dilute.3,6 Thus the result of a single UGAG assay is insufficient to either confirm or rule out a diagnosis of MPS. Retesting is justified if clinical suspicion remains high even when the UGAG result is negative.1


  1. 1.Burton BK, Giugliani R. (2012) Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr 171(4): 631-639.
  2. 2.Lehman TJ, Miller N, Norquist B, Underhill L, Keutzer J. (2011) Diagnosis of the mucopolysaccharidoses. Rheumatology (Oxford) 50 Suppl 5: v41-48.
  3. 3.Muenzer J. (2011) Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 50 Suppl 5: v4-12.
  1. 4.Randall DR, Colobong KE, Hemmelgarn H, et al. (2008) Heparin cofactor II-thrombin complex: a biomarker of MPS disease. Mol Genet Metab 94(4): 456-461.
  2. 5.Langford-Smith KJ, Mercer J, Petty J, et al. (2011) Heparin cofactor II-thrombin complex and dermatan sulphate:chondroitin sulphate ratio are biomarkers of short- and long-term treatment effects in mucopolysaccharide diseases. J Inherit Metab Dis 34(2): 499-508.
  3. 6.Cimaz R, La Torre F. (2014) Mucopolysaccharidoses. Curr Rheumatol Rep 16(1): 389.