Detecting multiple lysosomal storage diseases by tandem mass spectrometry — A national newborn screening program in Taiwan

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. 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. 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. 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. •We reported the largest sample size of Fabry, Pompe, Gaucher and MPS I screening.•MS/MS for multiple lysosomal enzymes can be introduced into newborn screening.•MS/MS method has positive predictive values equal to or better than current assay.•According to NBS, early detection and treatment are beneficial for LSD patients.