Performance of the dimethylmethylene blue test for the diagnosis of mucopolysaccharidoses

Abstract

The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders resulting from inherited defects in the breakdown of glycosaminoglycans (GAG). Affected children develop progressive connective tissue changes and/or progressive psychomotor retardation. Treatment is available for some disorders and is most effective when started early. Early manifestations are non-specific and diagnosis is usually reliant on the finding of an increased GAG excretion performed as part of a metabolic screen, using a dye binding assay with dimethylmethylene blue (DMB). Some reports have questioned the reliability of this technique for detecting MPS disorders. We have performed this test since 1997 and present a review of the performance of the assay in our hands. Results Over 70,000 urines have been tested with 54 confirmed positive cases (14 MPS I, 14 MPS II, 21 MPS III, 2 MPS IV, 2 MPS VI and 1 MPS VII). One MPS III patient had a result at the upper limit of normal and one adult patient with MPS IV had a result in the normal range. The remainder were all clearly abnormal. Conclusion The DMB test is a reliable first line investigation for MPS but negative results should be reported with a comment regarding discussion with the laboratory if there are strong clinical suspicions of an MPS disorder.