TY - JOUR
T1 - Profiling oligosaccharidurias by electrospray tandem mass spectrometry
T2 - Quantifying reducing oligosaccharides
AU - Ramsay, Steven L.
AU - Meikle, Peter J.
AU - Hopwood, John J.
AU - Clements, Peter R.
N1 - Funding Information:
The financial support of Pharming, TLH Research, and the National Health and Medical Research Council of Australia is gratefully acknowledged. We also thank Julie Bielicki and Barbara King (Women’s and Children’s Hospital, Adelaide, Australia) for the donation of recombinant enzymes.
PY - 2005/10/1
Y1 - 2005/10/1
N2 - A method to semiquantify urinary oligosaccharides from patients suffering from oligosaccharidurias is presented. l-Phenyl-3-methyl-5-pyrazolone has been used to derivatize urinary oligosaccharides prior to analysis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Disease-specific oligosaccharides were identified for several oligosaccharidurias, including GM1 gangliosidosis, GM2 gangliosidosis, sialic acid storage disease, sialidase/neuraminidase deficiency, galactosialidosis, I-cell disease, fucosidosis, Pompe and Gaucher diseases, and α-mannosidosis. The oligosaccharides were referenced against the internal standard, methyl lactose, to produce ratios for comparison with control samples. Elevations in specific urinary oligosaccharides were indicative of lysosomal disease and the defective catabolic enzyme. This method has been adapted to enable assay of large sample numbers and could readily be extended to other oligosaccharidurias and to monitor oligosaccharide levels in patients receiving treatment. It also has immediate potential for incorporation into a newborn screening program.
AB - A method to semiquantify urinary oligosaccharides from patients suffering from oligosaccharidurias is presented. l-Phenyl-3-methyl-5-pyrazolone has been used to derivatize urinary oligosaccharides prior to analysis by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Disease-specific oligosaccharides were identified for several oligosaccharidurias, including GM1 gangliosidosis, GM2 gangliosidosis, sialic acid storage disease, sialidase/neuraminidase deficiency, galactosialidosis, I-cell disease, fucosidosis, Pompe and Gaucher diseases, and α-mannosidosis. The oligosaccharides were referenced against the internal standard, methyl lactose, to produce ratios for comparison with control samples. Elevations in specific urinary oligosaccharides were indicative of lysosomal disease and the defective catabolic enzyme. This method has been adapted to enable assay of large sample numbers and could readily be extended to other oligosaccharidurias and to monitor oligosaccharide levels in patients receiving treatment. It also has immediate potential for incorporation into a newborn screening program.
KW - 1-Phenyl-3-methyl-5-pyrazolone
KW - Electrospray ionization-tandem mass spectrometry
KW - G gangliosidosis
KW - I-cell
KW - Lysosomal storage disorder
KW - Oligosacchariduria
KW - Pompe
KW - Sandhoff
KW - Sialidosis
KW - Tay-Sachs
KW - α-Mannosidosis
UR - http://www.scopus.com/inward/record.url?scp=27644456157&partnerID=8YFLogxK
U2 - 10.1016/j.ab.2005.06.042
DO - 10.1016/j.ab.2005.06.042
M3 - Article
C2 - 16111643
AN - SCOPUS:27644456157
SN - 0003-2697
VL - 345
SP - 30
EP - 46
JO - Analytical Biochemistry
JF - Analytical Biochemistry
IS - 1
ER -