Expert recommendations for the laboratory diagnosis of MPS VI.

TY - JOUR

T1 - Expert recommendations for the laboratory diagnosis of MPS VI.

AU - Wood, T

AU - Bodamer, O A

AU - Burin, M G

AU - D'Almeida, V

AU - Fietz, M

AU - Giugliani, R

AU - Hawley, S M

AU - Hendriksz, C J

AU - Hwu, W L

AU - Ketteridge, D

AU - Lukacs, Zoltan

AU - Mendelsohn, N J

AU - Miller, N

AU - Pasquali, M

AU - Schenone, A

AU - Schoonderwoerd, K

AU - Winchester, B

AU - Harmatz, P

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Humans

KW - Cerebroside-Sulfatase/blood/urine

KW - Dried Blood Spot Testing

KW - Glycosaminoglycans/urine

KW - Mucopolysaccharidosis VI/diagnosis/enzymology

KW - N-Acetylgalactosamine-4-Sulfatase/blood/genetics/urine

KW - Humans

KW - Cerebroside-Sulfatase/blood/urine

KW - Dried Blood Spot Testing

KW - Glycosaminoglycans/urine

KW - Mucopolysaccharidosis VI/diagnosis/enzymology

KW - N-Acetylgalactosamine-4-Sulfatase/blood/genetics/urine

M3 - SCORING: Journal article

VL - 106

SP - 73

EP - 82

JO - MOL GENET METAB

JF - MOL GENET METAB

SN - 1096-7192

IS - 1

M1 - 1

ER -