Detecting multiple lysosomal storage diseases by tandem mass spectrometry--a national newborn screening program in Taiwan

Clin Chim Acta. 2014 Apr 20:431:80-6. doi: 10.1016/j.cca.2014.01.030. Epub 2014 Feb 7.


Background: Interest in lysosomal storage diseases in newborn screening programs has increased in recent years. Two techniques, fluorescence (4-MU) and tandem mass spectrometry (MS/MS) methods are frequently used. We report a pilot study of large scale newborn screening for Fabry, Pompe, Gaucher, and MPS I diseases by using the MS/MS method in Taiwan and compared the performance of the MS/MS with 4-MU methods.

Methods: More than 100,000 dried blood spots (DBSs) were collected consecutively as part of the national Taiwan newborn screening programs. The enzyme activities were detected by the MS/MS method from a DBS punch. Mutation analysis was further performed for newborns with detected enzyme deficiency.

Results: The DNA sequence analysis for suspected cases revealed 64 newborns with confirmed Fabry mutations, 16 were classified as infantile or late-onset Pompe disease, and 1 was characterized as Gaucher disease. The positive predict value increased from 4.0% to 7.1% in the Pompe study, and from 61.0% to 95.5% in the Fabry study by the MS/MS method compared to 4-MU assay.

Conclusions: The MS/MS method has been validated as a more specific, powerful and efficient tool than the 4-MU assay. It also provided a multiplex solution of newborn screening for lysosomal storage diseases.

Keywords: Fabry disease; Gaucher disease; Lysosomal storage disease; Newborn screening; Pompe disease; Tandem mass spectrometry.

Publication types

  • Multicenter Study

MeSH terms

  • DNA / genetics
  • Dried Blood Spot Testing
  • Fabry Disease / diagnosis
  • Fabry Disease / genetics
  • Female
  • Gaucher Disease / diagnosis
  • Gaucher Disease / genetics
  • Glycogen Storage Disease Type II / diagnosis
  • Glycogen Storage Disease Type II / genetics
  • Humans
  • Infant, Newborn
  • Lysosomal Storage Diseases / diagnosis*
  • Male
  • Neonatal Screening
  • Pilot Projects
  • Quality Control
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Taiwan
  • Tandem Mass Spectrometry


  • DNA