Improved Reagents for Newborn Screening of Mucopolysaccharidosis Types I, II, and VI by Tandem Mass Spectrometry

CHENNAMANENI, NK, AB KUMAR, M BARCENAS, Zdeněk SPÁČIL, CR SCOTT, F TURECEK and MH GELB. Improved Reagents for Newborn Screening of Mucopolysaccharidosis Types I, II, and VI by Tandem Mass Spectrometry. Analytical Chemistry. WASHINGTON: AMER CHEMICAL SOC, 2014, vol. 86, No 9, p. 4508-4514. ISSN 0003-2700. Available from: https://dx.doi.org/10.1021/ac5004135.

Basic information

• Original name: Improved Reagents for Newborn Screening of Mucopolysaccharidosis Types I, II, and VI by Tandem Mass Spectrometry
• Authors: CHENNAMANENI, NK, AB KUMAR, M BARCENAS, Zdeněk SPÁČIL, CR SCOTT, F TURECEK and MH GELB.
• Edition: Analytical Chemistry, WASHINGTON, AMER CHEMICAL SOC, 2014, 0003-2700.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 5.636
• Doi: http://dx.doi.org/10.1021/ac5004135
• UT WoS: 000335719900062

Abstract

Tandem mass spectrometry for the multiplex and quantitative analysis of enzyme activities in dried blood spots on newborn screening cards has emerged as a powerful technique for early assessment of lysosomal storage diseases. Here we report the design and process-scale synthesis of substrates for the enzymes alpha-L-iduronidase, iduronate-2-sulfatase, and N-acetylgalactosamine-4-sulfatase that are used for newborn screening of mucopolysaccharidosis types I, II, and VI. The products contain a bisamide unit that is hypothesized to readily protonate in the gas phase, which improves detection sensitivity by tandem mass spectrometry. The products contain a benzoyl group, which provides a useful site for inexpensive deuteration, thus facilitating the preparation of internal standards for the accurate quantification of enzymatic products. Finally, the reagents are designed with ease of synthesis in mind, thus permitting scale-up preparation to support worldwide newborn screening of lysosomal storage diseases. The new reagents provide the most sensitive assay for the three lysosomal enzymes reported to date as shown by their performance in reactions using dried blood spots as the enzyme source. Also, the ratio of assay signal to that measured in the absence of blood (background) is superior to all previously reported mucopolysaccharidosis types I, II, and VI assays.