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01.12.2017 | Review | Ausgabe 1/2017 Open Access

Orphanet Journal of Rare Diseases 1/2017

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

Orphanet Journal of Rare Diseases > Ausgabe 1/2017
Chris Stinton, Julia Geppert, Karoline Freeman, Aileen Clarke, Samantha Johnson, Hannah Fraser, Paul Sutcliffe, Sian Taylor-Phillips
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The online version of this article (doi:10.​1186/​s13023-017-0599-z) contains supplementary material, which is available to authorized users.



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.


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.


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.


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.
Additional file 1: Supplement 1 Search strategy for Ovid Medline (26th January 2016). Supplement 2 QUADAS-2 checklist. Supplement 3 Modified QUADAS-2 and guidance notes for tyrosinaemia type 1 screening. Supplement 4 Excluded studies (n=66). Supplement 5 Risk of bias and applicability concerns summary: review authors' judgements about each domain for each included study. Supplement 6 Study characteristics and MS/MS screening methodology for Tyrosinemia type 1. (DOCX 78 kb)
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