Recent developments and new applications of tandem mass spectrometry in newborn screening

Curr Opin Pediatr. 2004 Aug;16(4):427-33. doi: 10.1097/01.mop.0000133635.79661.84.


Purpose of review: To summarize recent developments in the field of newborn screening related to the use of tandem mass spectrometry as an analytic platform.

Recent findings: Novel inborn errors of metabolism with informative amino acid and/or acylcarnitine profiles have been characterized, increasing the complexity of the differential diagnosis of abnormal results. In addition, methods have been developed for the analysis in dried blood spots of steroids and lysosomal enzymes. Previously unrecognized genotype/phenotype correlations have been found among cohorts of patients whose conditions were diagnosed by screening rather than clinically. Several government entities and professional organizations have issued position statements on newborn screening, and worldwide outcome studies continue to underscore the clinical and financial benefits of expanded newborn screening.

Summary: Although it is done inconsistently, newborn screening in the United States is undergoing a rapid expansion driven by the introduction of tandem mass spectrometry in at least 34 state programs. This technology is also used to detect disease markers beyond acylcarnitines and amino acids, as both primary and second-tier tests. In addition to analytic improvements, there is a trend toward the development of joint programs not limited to contiguous geographic areas, often based upon public-private partnerships. This review will summarize several new developments in the field that have occurred since early 2003 and will mention others likely to occur in the near future.

Publication types

  • Review

MeSH terms

  • Adrenal Hyperplasia, Congenital / diagnosis
  • Adrenal Hyperplasia, Congenital / etiology
  • Calcium-Binding Proteins / deficiency
  • Calcium-Binding Proteins / metabolism
  • Humans
  • Infant, Newborn
  • Malonates / metabolism
  • Mass Screening / methods*
  • Mass Spectrometry / methods
  • Metabolism, Inborn Errors / diagnosis*
  • Metabolism, Inborn Errors / etiology
  • Neonatal Screening / methods*
  • Organic Anion Transporters / deficiency
  • Organic Anion Transporters / metabolism
  • Oxidoreductases / deficiency
  • Oxidoreductases / metabolism
  • Predictive Value of Tests


  • Calcium-Binding Proteins
  • Malonates
  • Organic Anion Transporters
  • citrin
  • ethylmalonic acid
  • Oxidoreductases