title: Newborn screening for Tyrosinemia type 1 using succinylacetone - a systematic review of test accuracy.
abstract: 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.
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, England.
authors.forename: Chris
authors.initials: C
authors.lastname: Stinton
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, England.
authors.forename: Julia
authors.initials: J
authors.lastname: Geppert
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, England.
authors.forename: Karoline
authors.initials: K
authors.lastname: Freeman
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, England.
authors.forename: Aileen
authors.initials: A
authors.lastname: Clarke
authors.affiliation: Warwick Library, University of Warwick, Coventry, CV4 7AL, England.
authors.forename: Samantha
authors.initials: S
authors.lastname: Johnson
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, England.
authors.forename: Hannah
authors.initials: H
authors.lastname: Fraser
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, England.
authors.forename: Paul
authors.initials: P
authors.lastname: Sutcliffe
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, CV4 7AL, England. S.Taylor-Phillips@warwick.ac.uk.
authors.forename: Sian
authors.initials: S
authors.lastname: Taylor-Phillips
mesh_terms: D006537:Heptanoates / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D008661:Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis; D015997:Neonatal Screening / Q000379:methods; D053719:Tandem Mass Spectrometry; D020176:Tyrosinemias / Q000097:blood* / Q000175:diagnosis*
chemical_list: D006537:Heptanoates; C020804:succinylacetone
keywords: Inborn errors of metabolism; Newborn blood spot screening; Succinylacetone; Systematic review; Tandem mass spectrometry; Test accuracy; Tyrosinemia