Identification of infants at risk for developing Fabry, Pompe, or mucopolysaccharidosis-I from newborn blood spots by tandem mass spectrometry

J Pediatr. 2013 Aug;163(2):498-503. doi: 10.1016/j.jpeds.2013.01.031. Epub 2013 Mar 1.


Objective: To assess the performance of a tandem mass spectrometry (MS/MS) technology in a newborn screening laboratory to simultaneously measure α-galactosidase, acid-α-glucosidase, and α-L-iduronidase for the detection of infants at risk to develop Fabry, Pompe, or mucopolysaccharidosis (MPS)-I diseases.

Study design: Enzyme activity was assayed from a 3.2-mm punch from 100,000+ anonymous newborn blood spots. Punches with low enzyme activity were further evaluated by nucleotide sequence analysis of the responsible gene. Confirmation of affected infants was dependent on identification of mutations compatible with diminished enzyme activity.

Results: The technology for simultaneously measuring multiple enzyme activities by MS/MS was successful. The confirmation of diagnosis for Fabry, Pompe, or MPS-I, by DNA sequencing estimated the prevalence of Fabry disease at 1/7800 males (95% CI 1/17,800-1/3600); Pompe disease at 1/27,800 newborns (95% CI 1/90,000-1/10,200); and MPS-I at 1/35,500 newborns (95% CI 1/143,000-1/11,100). These estimates of prevalence are 2 to 4 times greater than the prevalence estimated by clinical diagnosis. The combined prevalence for the 3 disorders was 1/7500 newborns (95% CI 1/13,500-1/4500).

Conclusions: MS/MS for the simultaneous assay of multiple lysosomal enzymes can be successfully introduced into a routine newborn screening laboratory. The technology has a positive predictive value equal to, or better, than methods currently used for the detection of nonlysosomal disorders. Using newborn blood spots, the combined prevalence of Fabry, Pompe, and MPS-I is estimated at 1/7500 newborns based on low-enzyme activity and confirmation by mutation analysis.

Keywords: CDC; Centers for Disease Control and Prevention; GAA; GLA; IDUA; LSD; Lysosomal storage disease; MPS; MS/MS; Mucopolysaccharidosis; PCR; Polymerase chain reaction; QC; Quality control; Tandem mass spectrometry; α-L-iduronidase; α-galactosidase; α-glucosidase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fabry Disease / blood*
  • Fabry Disease / diagnosis
  • Female
  • Glycogen Storage Disease Type II / blood*
  • Glycogen Storage Disease Type II / diagnosis
  • Humans
  • Infant, Newborn
  • Male
  • Mucopolysaccharidosis I / blood*
  • Mucopolysaccharidosis I / diagnosis
  • Neonatal Screening / methods*
  • Risk Factors
  • Tandem Mass Spectrometry*