Abstract
Tandem mass spectrometry has been used for determinations of enzyme activities in biological samples. Activities in rehydrated dried blood spots of lysosomal enzymes glucocerebrosidase, acid sphingomyelinase, galactocerebroside β-galactosidase, acid-α-galactosidase, acid α-glucosidase, and α-D-iduronidase are measured simultaneously by multiple-reaction monitoring of ion dissociations from cations produced by electrospray ionization of enzymatic products. Simple and inexpensive assay protocols are described that are readily adopted for handling multiple samples in 96-well microtiter plates, employing simple separation steps, and using less than or equal to 3 µmol of synthetic or commercially available substrates, and less than 25 nmol of internal standards per analysis. The assays have the potential of being used for large-scale screening of newborns for the detection of inborn errors of metabolism.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Koeberl, D. D., Young, S. P., Gregersen, N. S., et al. (2003) Rare disorders of metabolism with elevated butyryl-and isobutyryl-carnitine detected by tandem mass spectrometry. Pediatr. Res. 54, 219–223.
Stevens, R. D., Hillman, S. L., Worthy, S., Sanders, D., and Millington, D. S. (2000) Assay for free and total carnitine in human plasma using tandem mass spectrometry. Clin. Chem. 46, 727–729.
Fauler, G., Leis, H. J., Huber, E., et al. (1997) Determination of homovanillic acid and vanillylmandelic acid in neuroblastoma screening by stable isotope dilution GC-MS. J. Mass Spectrom. 32, 507–514.
Cole, R. B. (ed.) (1997) Electrospray Ionization Mass Spectrometry. Fundamentals, Instrumentation and Applications, Wiley-Interscience, New York.
Busch, K. L., Glish, G. L., and McLuckey, S. A. (eds.) (1988) Mass Spectrometry/Mass Spectrometry: Techniques and Applications of Tandem Mass Spectrometry, VCH Publishers, New York.
Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D. (eds.) (2001) Lysosomal Storage Disorders. In: The Metabolic & Molecular Bases of Inherited Disease, 8th Ed., McGraw-Hill, New York, Part 16, pp. 3371–3896.
Sandhoff, K., Kolter, T., and Harzer, K. (2001) Sphingolipid activator proteins. In: The Metabolic & Molecular Bases of Inherited Disease, 8th Ed., (Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds.) McGraw-Hill, New York, pp. 3371–3375.
Neufeld, E. F. and Muenzer, J. (2001) The mucopolysaccharidoses. In: The Metabolic & Molecular Bases of Inherited Disease, 8th Ed., (Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds.) McGraw-Hill, New York, pp. 3421–3426.
Gerber, S. A., Scott, C. R., Tureček, F., and Gelb, M. H. (1999) Analysis of rates of multiple enzymes in cell lysates by electrospray ionization mass spectrometry. J. Am. Chem. Soc. 121, 1102–1104.
Tureček, F. (2002) Mass spectrometry in coupling with affinity capture-release and isotope-coded affinity tags for quantitative protein analysis. J. Mass Spectrom. 37, 1–14.
Gerber, S.A., Scott, C. R., Tureček, F., and Gelb, M. H. (2001) Direct profiling of multiple enzyme activities in human cell lysates by affinity chromatography/electrospray ionization mass spectrometry. Anal. Chem. 73, 1651–1657.
Zhou, X.-F., Tureček, F., Scott, C. R., and Gelb, M. H. (2001) Quantitation of cellular acid sphingomyelinase and galactocerebroside-galactosidase activities by electrospray ionization mass spectrometry. Clin. Chem. 45, 874–881.
Li, Y., Ogata, Y., Freeze, H. H., Scott, C. R., Turecek, F., and Gelb, M. H. (2003) Affinity capture and elution/electrospray ionization mass spectrometry assay of phosphomannomutase and phosphomannose isomerase for the multiplex analysis of congenital disorders of glycosylation yypes Ia and Ib. Anal. Chem. 75, 42–48.
Li, Y., Scott, C. R., Chamoles, N. A., et al. (2004) Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin. Chem. 50, 1785–1796.
Li, Y., Brockmann, K., Tureček, F., Scott, C. R., and Gelb, M. H. (2004) Tandem mass spectrometry for the direct assay of enzymes in dried blood spots: application to newborn screening for Krabbe disease. Clin. Chem. 50, 638–640.
For the nomenclature of mass spectrometric techniques, see the Mass Spectrometry Terms and Definitions Project at http://www.msterms.com/wiki/index.
Wang, D., Eadala, B., Sadilek, M., et al. (2005) Tandem mass spectrometric analysis of dried blood spots for screening of mucopolysaccharidosis I in newborns. Clin. Chem. 51, 898–900.
Dacie, J. V. and Lewis, S. M. (1984) Practical Haematology, 6th Ed., Churchill Livingstone, Edinburgh, Scotland, pp. 9.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this protocol
Cite this protocol
Tureček, F., Scott, C.R., Gelb, M.H. (2007). Tandem Mass Spectrometry in the Detection of Inborn Errors of Metabolism for Newborn Screening. In: Sechi, S. (eds) Quantitative Proteomics by Mass Spectrometry. Methods in Molecular Biology, vol 359. Humana Press. https://doi.org/10.1007/978-1-59745-255-7_10
Download citation
DOI: https://doi.org/10.1007/978-1-59745-255-7_10
Publisher Name: Humana Press
Print ISBN: 978-1-58829-571-2
Online ISBN: 978-1-59745-255-7
eBook Packages: Springer Protocols