Expert recommendations for the laboratory diagnosis of MPS VI
Journal
Molecular Genetics and Metabolism
Journal Volume
106
Journal Issue
1
Pages
73-82
Date Issued
2012
Author(s)
Wood T.
Bodamer O.A.
Burin M.G.
D'Almeida V.
Fietz M.
Giugliani R.
Hawley S.M.
Hendriksz C.J.
Ketteridge D.
Lukacs Z.
Mendelsohn N.J.
Miller N.
Pasquali M.
Schenone A.
Schoonderwoerd K.
Winchester B.
Harmatz P.
Abstract
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. ? 2012 Elsevier Inc.
Subjects
Algorithm; Arylsulfatase B; Diagnosis; Glycosaminoglycan; Maroteaux-Lamy syndrome; MPS VI
SDGs
Other Subjects
dermatan sulfate; glycosaminoglycan; n acetylgalactosamine 4 sulfatase; article; blood sampling; dried blood spot testing; electrophoretic mobility; enzyme activity; enzyme linked immunosorbent assay; genetic counseling; human; immunofluorescence test; ion exchange chromatography; laboratory diagnosis; leukocyte; liquid chromatography; Maroteaux Lamy syndrome; multiple sulfatase deficiency; priority journal; punch biopsy; spectrophotometry; tandem mass spectrometry; urinalysis; Cerebroside-Sulfatase; Dried Blood Spot Testing; Glycosaminoglycans; Humans; Mucopolysaccharidosis VI; N-Acetylgalactosamine-4-Sulfatase
Type
journal article