Expert recommendations for the laboratory diagnosis of MPS VI

• Published in: Molecular genetics and metabolism Vol. 106; no. 1; pp. 73 - 82
• Main Authors: Wood, T., Bodamer, O.A., Burin, M.G., D'Almeida, V., Fietz, M., Giugliani, R., Hawley, S.M., Hendriksz, C.J., Hwu, W.L., Ketteridge, D., Lukacs, Z., Mendelsohn, N.J., Miller, N., Pasquali, M., Schenone, A., Schoonderwoerd, K., Winchester, B., Harmatz, P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2012
• Subjects: Algorithm; Algorithms; Arylsulfatase; Arylsulfatase B; Cerebroside-Sulfatase - blood; Cerebroside-Sulfatase - urine; Diagnosis; Dried Blood Spot Testing; Enzymes; Glycosaminoglycan; Glycosaminoglycans; Glycosaminoglycans - urine; Humans; lysosomal storage diseases; Maroteaux-Lamy syndrome; MPS VI; Mucopolysaccharidosis VI - diagnosis; Mucopolysaccharidosis VI - enzymology; N-Acetylgalactosamine; N-Acetylgalactosamine-4-Sulfatase - blood; N-Acetylgalactosamine-4-Sulfatase - genetics; N-Acetylgalactosamine-4-Sulfatase - urine; Sulfate; Therapeutic applications; Urine; MPS VI; Glycosaminoglycan; Arylsulfatase B; Maroteaux–Lamy syndrome; Diagnosis; Algorithm
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2012.02.005

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B, ASB). This enzyme is required for the degradation of dermatan sulfate. In its absence, dermatan sulfate accumulates in cells and is excreted in large quantities in urine. Specific therapeutic intervention is available; however, accurate and timely diagnosis is crucial for maximal benefit. To better understand the current practices for diagnosis and to establish diagnostic guidelines, an international MPS VI laboratory diagnostics scientific summit was held in February of 2011 in Miami, Florida. The various steps in the diagnosis of MPS VI were discussed including urinary glycosaminoglycan (uGAG) analysis, enzyme activity analysis, and molecular analysis. The following conclusions were reached. Dilute urine samples pose a significant problem for uGAG analysis and MPS VI patients can be missed by quantitative uGAG testing alone as dermatan sulfate may not always be excreted in large quantities. Enzyme activity analysis is universally acknowledged as a key component of diagnosis; however, several caveats must be considered and the appropriate use of reference enzymes is essential. Molecular analysis supports enzyme activity test results and is essential for carrier testing, subsequent genetic counseling, and prenatal testing. Overall the expert panel recommends caution in the use of uGAG screening alone to rule out or confirm the diagnosis of MPS VI and acknowledges enzyme activity analysis as a critical component of diagnosis. Measurement of another sulfatase enzyme to exclude multiple sulfatase deficiency was recommended prior to the initiation of therapy. When feasible, the use of molecular testing as part of the diagnosis is encouraged. A diagnostic algorithm for MPS VI is provided. ► A panel of experts provides an overview of MPS VI laboratory testing and a diagnostic algorithm. ► Quantitative and qualitative urinary GAG assays should be run in parallel and are not diagnostic. ► ASB activity is the gold standard test: Confirm sample integrity, rule out MSD/I-cell disease. ► Multiple samples and multiple tests are recommended to reach an accurate diagnosis. ► Maintain high clinical suspicion of MPS: Retest if necessary, communicate openly with lab.