The definitive diagnostic test for MPS disorders is measurement of enzyme activity. The enzyme assay is performed at specialised testing facilities using cultured fibroblasts, leukocytes, plasma, or serum as the enzyme source.1,2
Demonstration of absent or deficient activity of the relevant enzyme confirms a diagnosis of MPS I (α-L-iduronidase) or MPS II (iduronate-2-sulphatase).3 Activity of another sulfatase is measured when a sulfatase deficiency is found, to rule out multiple sulfatase deficiency.3 Patients with signs and symptoms suggestive of MPS I/MPS II and normal test results should be referred to a clinical geneticist to rule out other lysosomal storage disorders (LSDs).4
Mutation analysis to identify the disease-causing mutations usually follows when a diagnosis of MPS I or MPS II is confirmed by enzyme assay.2 It can provide useful prognostic information (learn more in Genetics) and enables family screening to detect carriers.
The enzyme assay cannot be used to detect carriers in a family affected by MPS I/MPS II as the levels of enzyme activity in carriers overlap with that seen in non-affected individuals. Therefore, mutation analysis is the only reliable method available to detect carriers.1,2 Mutation analysis is also the most reliable method of confirming diagnosis in rare cases of females with MPS II (See Genetics).5