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

Abstract

BackgroundTyrosinemia 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.MethodsWe 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.ResultsTen 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.ConclusionsScreening 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0599-z) contains supplementary material, which is available to authorized users.

Metabolomics to Improve the Diagnostic Efficiency of Inborn Errors of Metabolism

“…Although the mass spectrometry-based enzymology has the benefit of scalability and the ability to easily add additional disorders, the digital microfluidics presents an attractive, cost-effective option [36]. Metabolite analysis can also be considered, such as succinylacetone in tyrosinemia type 1 [37] and glucosylsphingosine in Gaucher disease [38]. Another typical example would be differentiating sub-types of hyperphenylalaninemia, where pterin profiling would be undertaken for differentiating causes related to pterin metabolism from phenylalanine hydroxylase since treatment is different.…”

Comparison of a full systematic review versus rapid review approaches to assess a newborn screening test for tyrosinemia type 1

“…Details of the full results of the SR are published elsewhere. 16 3 | RESULTS Figure 1 provides the PRISMA flow diagram for the basic REA, enhanced REA, and SR searches. We identified 310 unique records in each of the basic and enhanced REAs, and 1274 in the SR.…”

Evaluation of pre-symptomatic nitisinone treatment on long-term outcomes in Tyrosinemia type 1 patients: a systematic review

“…To justify the introduction of newborn blood spot (NBS) screening programmes for TYR1, there should be evidence that, next to a simple, safe, precise and validated screening test, treatment at a pre-symptomatic phase leads to better outcomes for the screened individual compared to treatment initiation following symptomatic detection. We have recently published a linked review regarding the current state of evidence relating to the test accuracy of newborn screening for TYR1 using SUAC as primary marker that highlights important limitations in the literature [ 15 ]. To date, no study has synthesized and quality appraised all of the available evidence regarding early and late treatment of TYR1 with nitisinone.…”