Accurate determination of an MPS disorder has never been more important
Early discernment of specific enzyme deficiencies and resulting definitive diagnosis can lead to early intervention if enzyme replacement therapy (ERT) is available.2,24,25 Even when ERT is not available, disease-specific management can optimise patient outcomes.2 When MPS is suspected, a comprehensive enzyme panel is warranted.1 Detection of enzyme deficiencies relies on the measurement of enzyme activity in fibroblasts or leukocytes, which is the recommended method for confirming diagnosis.26 A comprehensive overview of the path to diagnosis of MPS VI is outlined below.
Diagnostic testing paradigm in MPS VI
Clinical and/or radiographic suspicion of MPS VI
Discuss testing with family
Select a screening option
- DBS testing may be used in screening; current gold standard for diagnosis is leukocyte or fibroblast samples
- Multiplex assays to screen for multiple lysosomal disorders are now available
- Measurement of multiple enzymes required to rule out multiple enzyme deficiencies and lysosomal trafficking problems
- Reference lysosomal enzyme should be assayed at same time to confirm sample integrity
- Minimise blood sample shipment times; next-day arrival is recommended
- When ASB activity is low, a second sulphatase must be measured to rule out multiple sulphatase deficiency
- May rule in but cannot rule out MPS
- Slowly progressing patients may have normal or only mildly elevated uGAGs
- Elevated uGAGs may be missed in dilute urine samples
- Should be quantitative and qualitative: quantitative elevation of total uGAG and qualitative elevation of dermatan sulfate
- First morning void of 10-20 mL considered optimal
- Urine shipped frozen or via dried filter paper
- Pay close attention to units and reference ranges
- Comparison of uGAG test results from multiple laboratories may not be valid due to multiple assay methods in common use

Diagnostic test for MPS VI
ASB activity measurement in leukocyte or fibroblast samples (gold standard)
- Low ASB activity
- Reference lysosomal enzyme should be assayed at same time to confirm sample integrity
- When ASB activity is low, a second sulphatase must be measured to rule out multiple sulphatase deficiency
- If using a fibroblast sample, a mannose 6-phosphate-guided reference enzyme must be measured to rule out I-cell disease
Additional testing options
- Confirmation of low ASB enzyme activity by repeat measurement on separate sample or tissue
- When feasible, identification of 2 pathogenic mutations in the arylsulfatase B (ARSB) gene (1 from each parent)
A basic algorithm depicting the tests that can be used for diagnostic confirmation of Morquio A (MPS IVA) is shown below.
Diagnostic algorithm for Morquio A27

Enzyme panels to test for low activity across all 11 enzymes are available. This methodology can quickly and accurately assess enzymatic activity for key enzymes across multiple MPS and lysosomal storage disorders.1,26