Newborn screening for Tyrosinemia type 1 using succinylacetone - a systematic review of test accuracy

Orphanet J Rare Dis. 2017 Mar 9;12(1):48. doi: 10.1186/s13023-017-0599-z.


Background: Tyrosinemia type 1 is an autosomal recessive disorder of amino acid metabolism. Without treatment, death in childhood is common. Treatment with nitisinone and dietary restrictions are associated with improved outcomes; some studies suggest better outcomes when treatment begins at an asymptomatic stage. Newborn screening allows for earlier identification, but there is uncertainty regarding the test accuracy of the current method: succinylacetone measurement in dried blood spots using tandem mass spectrometry.

Methods: We conducted a systematic review of literature published up to January 2016. Two reviewers independently assessed titles, abstracts, full texts, and conducted quality appraisals. A single reviewer extracted data, which was checked by a second reviewer.

Results: Ten studies provided test accuracy data: five studies reporting screening experiences and five case-control studies. Sensitivity (29 cases in total) and specificity (34,403 controls in total) were 100% in the case-control studies, but could not be calculated in the studies reporting screening experiences due to a lack of follow-up of screen-negative babies. Positive predictive values in the screening experience studies ranged from 66.7% (2 true positive cases, 1 false positive case from ~500,000 people screened) to 100% (8 true positive cases from 856,671 people screened); negative predictive values could not be calculated. Positive and negative predictive values cannot be calculated from case-control studies.

Conclusions: Screening for Tyrosinemia type 1 using tandem mass spectrometry measurement of succinylacetone from dried blood spots appears to be promising. Confirmation of test accuracy data should be obtained from studies that include a two-year follow-up of individuals who screen negative.

Keywords: Inborn errors of metabolism; Newborn blood spot screening; Succinylacetone; Systematic review; Tandem mass spectrometry; Test accuracy; Tyrosinemia.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Heptanoates / blood*
  • Humans
  • Infant, Newborn
  • Metabolism, Inborn Errors / blood
  • Metabolism, Inborn Errors / diagnosis
  • Neonatal Screening / methods
  • Tandem Mass Spectrometry
  • Tyrosinemias / blood*
  • Tyrosinemias / diagnosis*


  • Heptanoates
  • succinylacetone