UGAG

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

References

  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.