Tandem mass spectrometry has a larger analytical range than fluorescence assays of lysosomal enzymes: Application to newborn screening and diagnosis of mucopolysaccharidoses types II, IVA, and VI

Arun Babu Kumar, Sophia Masi, Farideh Ghomashchi, Naveen Kumar Chennamaneni, Makoto Ito, C. Ronald Scott, Frantisek Turecek, Michael H. Gelb, Zdenek Spacil

Research output: Contribution to journalArticle

31 Citations (Scopus)


BACKGROUND: There is interest in newborn screening and diagnosis of lysosomal storage diseases because of the development of treatment options that improve clinical outcome. Assays of lysosomal enzymes with high analytical range (ratio of assay response from the enzymatic reaction divided by the assay response due to nonenzymatic processes) are desirable because they are predicted to lead to a lower rate of false positives in population screening and to more accurate diagnoses. METHODS: We designed new tandem mass spectrometry (MS/MS) assays that give the largest analytical ranges reported to date for the use of dried blood spots (DBS) for detection of mucopolysaccharidoses type II (MPS-II), MPS-IVA, and MPS-VI. For comparison, we carried out fluorometric assays of 6 lysosomal enzymes using 4-methylumbelliferyl (4MU)-substrate conjugates. RESULTS: The MS/MS assays for MPS-II, -IVA, and -VI displayed analytical ranges that are 1-2 orders of magnitude higher than those for the corresponding fluorometric assays. The relatively small analytical ranges of the 4MU assays are due to the intrinsic fluorescence of the 4MU substrates, which cause high background in the assay response. CONCLUSIONS: These highly reproducible MS/MS assays for MPS-II, -IVA, and -VI can support multiplex newborn screening of these lysosomal storage diseases. MS/MS assays of lysosomal enzymes outperform 4MU fluorometric assays in terms of analytical range. Ongoing pilot studies will allow us to gauge the impact of the increased analytical range on newborn screening performance.

Original languageEnglish
Pages (from-to)1363-1371
Number of pages9
JournalClinical Chemistry
Issue number11
Publication statusPublished - Nov 2015


All Science Journal Classification (ASJC) codes

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this