Screening newborns for inborn errors of metabolism by tandem mass spectrometry

N Engl J Med. 2003 Jun 5;348(23):2304-12. doi: 10.1056/NEJMoa025225.


Background: The recent development of electrospray tandem mass spectrometry makes it possible to screen newborns for many rare inborn errors of metabolism, but the efficacy and outcomes of screening remain unknown. We examined the effect of the screening of newborns by tandem mass spectrometry on the rates of diagnosis of 31 disorders.

Methods: We compared the rates of detection of 31 inborn errors affecting the metabolism of the urea cycle, amino acids, and organic acids and fatty-acid oxidation among 362,000 newborns screened by tandem mass spectrometry over a four-year period (April 1998 through March 2002) with the rates in six preceding four-year birth cohorts in New South Wales and the Australian Capital Territory, Australia, where screening, diagnostic, and clinical services were centralized.

Results: The overall prevalence of disorders during the periods when clinical diagnosis was used did not vary between 1982 and 1998. In the cohort screened with tandem mass spectrometry, the prevalence of inborn errors, excluding phenylketonuria, was 15.7 per 100,000 births (95 percent confidence interval, 11.9 to 20.4), as compared with adjusted rates of 8.6 to 9.5 per 100,000 births in the four preceding four-year cohorts. Of the 57 cases diagnosed after the introduction of newborn screening, 15 were diagnosed clinically; 7 of the 15 newborns had a normal result on screening. The rate of detection was increased specifically for medium-chain acyl-coenzyme A dehydrogenase deficiency (P<0.001) and other disorders of fatty-acid oxidation (P=0.007), as compared with the 16-year period before the implementation of neonatal screening for these disorders.

Conclusions: More cases of inborn errors of metabolism are diagnosed by screening with tandem mass spectrometry than are diagnosed clinically. It is not yet clear which patients with disorders diagnosed by such screening would have become symptomatic if screening had not been performed.

Publication types

  • Comparative Study

MeSH terms

  • Australian Capital Territory / epidemiology
  • Cohort Studies
  • Humans
  • Infant, Newborn
  • Mass Spectrometry* / methods
  • Metabolism, Inborn Errors / diagnosis*
  • Metabolism, Inborn Errors / epidemiology
  • Neonatal Screening / methods*
  • New South Wales / epidemiology
  • Prevalence