scholarly journals Preliminary Proficiency Testing Results for Succinylacetone in Dried Blood Spots for Newborn Screening for Tyrosinemia Type I

2009 ◽  
Vol 55 (12) ◽  
pp. 2207-2213 ◽  
Author(s):  
Barbara W Adam ◽  
Timothy H Lim ◽  
Elizabeth M Hall ◽  
W Harry Hannon
Keyword(s):  
Newborn Screening ◽  
Proficiency Testing ◽  
False Negative ◽  
Dried Blood Spots ◽  
Screening Tests ◽  
Type I ◽  
Primary Metabolite ◽  
Screening Practices ◽  
Tyrosinemia Type I ◽  
Stable Performance

Abstract Background: Succinylacetone (SUAC) is the primary metabolite accumulated in tyrosinemia type I—an inborn error of metabolism that, if untreated, can cause death from liver failure during the first months of life. Newborn screening laboratories measure SUAC in dried blood spot (DBS) samples to detect asymptomatic tyrosinemia type I. We used panels of SUAC-enriched DBSs to compare and evaluate the performance of these screening tests. Methods: We prepared sets of DBS materials enriched with predetermined SUAC concentrations and distributed samples of these materials, along with a screening practices questionnaire, to laboratories that perform SUAC tests. We compared their reported SUAC concentrations and questionnaire responses to identify screening practices that affect SUAC test outcomes. Results: Data from 2 pilot surveys showed large differences among laboratories in SUAC recoveries, reproducible within-laboratory recoveries, and stable performance of the DBS materials. Results from 257 proficiency test analyses contained a total of 6 false-negative misclassifications. Reported recoveries of added SUAC ranged from 0 to >200%. Low-biased SUAC recoveries were associated with 1 method used by 5 laboratories. All laboratories that reported SUAC recoveries ≥100% used DBS matrix calibrators. Conclusions: The wide ranges of SUAC concentrations reported for pilot and proficiency testing specimens demonstrate a need to harmonize quantitative results among laboratories. Although DBS matrix calibrators are important for optimizing SUAC recoveries, the preparation of these calibrators is not standardized among laboratories. Certified DBS-based SUAC calibrators are needed for accuracy and harmonization.

scholarly journals Combined Newborn Screening for Succinylacetone, Amino Acids, and Acylcarnitines in Dried Blood Spots

2008 ◽  
Vol 54 (4) ◽  
pp. 657-664 ◽  
Author(s):  
Coleman Turgeon ◽  
Mark J Magera ◽  
Pierre Allard ◽  
Silvia Tortorelli ◽  
Dimitar Gavrilov ◽  
...  
Keyword(s):  
Amino Acids ◽  
Newborn Screening ◽  
False Negative ◽  
Internal Standard ◽  
Early Death ◽  
Cost Effective ◽  
Dried Blood Spots ◽  
Type I ◽  
Blood Spots ◽  
Negative Results

Abstract Background: Tyrosinemia type I (TYR 1) is a disorder causing early death if left untreated. Newborn screening (NBS) for this condition is problematic because determination of the diagnostic marker, succinylacetone (SUAC), requires a separate first-tier or only partially effective second-tier analysis based on tyrosine concentration. To overcome these problems, we developed a new assay that simultaneously determines acylcarnitines (AC), amino acids (AA), and SUAC in dried blood spots (DBS) by flow injection tandem mass spectrometry (MS/MS). Methods: We extracted 3/16-inch DBS punches with 300 μL methanol containing AA and AC stable isotope-labeled internal standards. This extract was derivatized with butanol-HCl. In parallel, we extracted SUAC from the residual filter paper with 100 μL of a 15 mmol/L hydrazine solution containing the internal standard 13C5-SUAC. We combined the derivatized aliquots in acetonitrile for MS/MS analysis of AC and AA with additional SRM experiments for SUAC (m/z 155–137) and 13C5-SUAC (m/z 160–142). Analysis time was 1.2 min. Results: SUAC was increased in retrospectively analyzed NBS samples of 11 TYR 1 patients (length of storage, 52 months to 1 week; SUAC range, 13–81 μmol/L), with Tyr concentrations ranging from 65 to 293 μmol/L in the original NBS analysis. The mean concentration of SUAC in 13 521 control DBS was 1.25 μmol/L. Conclusion: The inclusion of SUAC analysis into routine analysis of AC and AA allows for rapid and cost-effective screening for TYR 1 with no tangible risk of false-negative results.

scholarly journals EDTA in Dried Blood Spots Leads to False Results in Neonatal Endocrinologic Screening

2008 ◽  
Vol 54 (3) ◽  
pp. 602-605 ◽  
Author(s):  
Ute Holtkamp ◽  
Jeanette Klein ◽  
Johannes Sander ◽  
Michael Peter ◽  
Nils Janzen ◽  
...  
Keyword(s):  
Newborn Screening ◽  
False Positive ◽  
Neonatal Screening ◽  
False Negative ◽  
Dried Blood Spots ◽  
Screening Tests ◽  
Blood Collection ◽  
Blood Spots ◽  
Sampling Procedures ◽  
Positive Results

Abstract Background: Blood samples for neonatal screening for inborn errors of metabolism are collected and shipped on standardized filter paper cards. Occasionally these samples are contaminated with EDTA, which is often used for anticoagulation. EDTA may interfere with newborn screening tests based on lanthanide fluorescence and thus lead to false-negative or false-positive results. Methods: We used tandem mass spectrometry (MS/MS) to detect EDTA in dried blood spots by use of an extra experiment that was integrated into the standard MS/MS neonatal screening and did not require an additional sample spot, nor extra time or work. We analyzed the influence of different blood sampling procedures on lanthanide fluorescence tests for thyroid-stimulating hormone (TSH) and 17-hydroxyprogesterone (17-OHP). Results: EDTA was increased in 138 of 190 000 newborn screening samples, 27 of which caused false- positive results in the immunoassay for 17-OHP. No false-negative TSH results were found. False-positive results in the 17-OHP test occurred when EDTA concentrations were >2.0 g/L; the TSH test, however, produced false negatives only when EDTA concentrations were >3.0 g/L. Using EDTA-containing devices the procedure of blood collection significantly influenced the concentration of the anticoagulant. Conclusion: Addition of EDTA quantification into standard MS/MS tests is a simple and useful method to avoid false-positive or false-negative neonatal screening results in lanthanide fluorescence–based tests.

Quantitative determination of succinylacetone in dried blood spots for newborn screening of tyrosinemia type I

2006 ◽  
Vol 88 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Mark J. Magera ◽  
Nishantha D. Gunawardena ◽  
Si Houn Hahn ◽  
Silvia Tortorelli ◽  
Grant A. Mitchell ◽  
...  
Keyword(s):  
Quantitative Determination ◽  
Newborn Screening ◽  
Dried Blood Spots ◽  
Type I ◽  
Blood Spots ◽  
Tyrosinemia Type I

scholarly journals Glutaric Aciduria Type I Missed by Newborn Screening: Report of Four Cases from Three Families

2021 ◽  
Vol 7 (2) ◽  
pp. 32
Author(s):  
Johannes Spenger ◽  
Esther M. Maier ◽  
Katharina Wechselberger ◽  
Florian Bauder ◽  
Melanie Kocher ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Biological Diversity ◽  
False Negative ◽  
Autosomal Recessive Disorder ◽  
Dried Blood Spots ◽  
Glutaric Aciduria Type ◽  
Type I ◽  
Gene Encoding ◽  
Glutaric Aciduria ◽  
Glutaric Aciduria Type I

Glutaric aciduria type I (GA-1) is a rare autosomal-recessive disorder of the degradation of the amino acids lysine and tryptophan caused by mutations of the GCDH gene encoding glutaryl-CoA-dehydrogenase. Newborn screening (NBS) for this condition is based on elevated levels of glutarylcarnitine (C5DC) in dried blood spots (DBS). Here we report four cases from three families in whom a correctly performed NBS did not detect the condition. Glutarylcarnitine concentrations were either normal (slightly below) or slightly above the cut-off. Ratios to other acylcarnitines were also not persistently elevated. Therefore, three cases were defined as screen negative, and one case was defined as normal, after a normal control DBS sample. One patient was diagnosed after an acute encephalopathic crisis, and the other three patients had an insidious onset of the disease. GA-1 was genetically confirmed in all cases. Despite extensive efforts to increase sensitivity and specificity of NBS for GA-1, by adjusting cut-offs and introducing various ratios, the biological diversity still leads to false-negative NBS results for GA-1.

scholarly journals The low excretor phenotype of glutaric acidemia type I is a source of false negative newborn screening results and challenging diagnoses

JIMD Reports ◽  
2021 ◽  
Author(s):  
Adam J. Guenzel ◽  
Patricia L. Hall ◽  
Anna I. Scott ◽  
Christina Lam ◽  
Irene J. Chang ◽  
...  
Keyword(s):  
Newborn Screening ◽  
False Negative ◽  
Type I ◽  
Glutaric Acidemia Type I

scholarly journals Spectrophotometric Microassay for δ-Aminolevulinate Dehydratase in Dried-Blood Spots as Confirmation for Hereditary Tyrosinemia Type I

2001 ◽  
Vol 47 (8) ◽  
pp. 1424-1429 ◽  
Author(s):  
Andreas Schulze ◽  
David Frommhold ◽  
Georg F Hoffmann ◽  
Ertan Mayatepek
Keyword(s):  
Enzyme Activity ◽  
Neonatal Screening ◽  
Dried Blood Spots ◽  
Confirmatory Test ◽  
Type I ◽  
Screening Programs ◽  
Blood Spots ◽  
Tyrosinemia Type I ◽  
Aminolevulinate Dehydratase ◽  
Hereditary Tyrosinemia

Abstract Background: Hereditary tyrosinemia type I (HT) fulfills the criteria for inclusion in neonatal screening programs, but measurement of tyrosine lacks clinical specificity and quantitative assay of succinylacetone is laborious. We developed a semiquantitative assay based on inhibition of δ-aminolevulinate dehydratase (ALA-D) by succinylacetone. Methods: Preincubation of 3-mm discs from dried-blood spots and reaction of the enzyme with δ-aminolevulinic acid as substrate were performed in microtiter plates. After separation of the supernatant and 10 min of color reaction with modified Ehrlich reagent, the formation of porphobilinogen was measured at 550 nm in a plate reader. Results: The detection limit for succinylacetone was 0.3 μmol/L; imprecision (CV) was <5.5% within-run and 10–16% between-run. Storage of blood spots at ambient temperature for several days led to a significant decrease of ALA-D activity. Enzyme activity was lost in filter cards at 45 °C, but remained stable at 2–37 °C. Enzyme activity was decreased in EDTA blood. The absorbance at 550 nm was 0.221 (± 0.073) in healthy neonates and 0.043–0.100 in 11 patients with HT. All neonates with increased tyrosine (above the 99.5th centile) in neonatal screening (97 of 47 000) had normal results by the new assay. Conclusions: The spectrophotometric microassay for ALA-D is a simple and sensitive test for HT. This represents a basis for further examination of its general reliability as a confirmatory test if tyrosine is found to be increased.

scholarly journals Incorporation of Second-Tier Biomarker Testing Improves the Specificity of Newborn Screening for Mucopolysaccharidosis Type I

2020 ◽  
Vol 6 (1) ◽  
pp. 10 ◽  
Author(s):  
Dawn S. Peck ◽  
Jean M. Lacey ◽  
Amy L. White ◽  
Gisele Pino ◽  
April L. Studinski ◽  
...  
Keyword(s):  
Newborn Screening ◽  
False Positive ◽  
Dermatan Sulfate ◽  
False Positive Rate ◽  
False Negative ◽  
Type I ◽  
Mucopolysaccharidosis Type ◽  
Mucopolysaccharidosis Type I ◽  
Second Tier ◽  
Mps I

Enzyme-based newborn screening for Mucopolysaccharidosis type I (MPS I) has a high false-positive rate due to the prevalence of pseudodeficiency alleles, often resulting in unnecessary and costly follow up. The glycosaminoglycans (GAGs), dermatan sulfate (DS) and heparan sulfate (HS) are both substrates for α-l-iduronidase (IDUA). These GAGs are elevated in patients with MPS I and have been shown to be promising biomarkers for both primary and second-tier testing. Since February 2016, we have measured DS and HS in 1213 specimens submitted on infants at risk for MPS I based on newborn screening. Molecular correlation was available for 157 of the tested cases. Samples from infants with MPS I confirmed by IDUA molecular analysis all had significantly elevated levels of DS and HS compared to those with confirmed pseudodeficiency and/or heterozygosity. Analysis of our testing population and correlation with molecular results identified few discrepant outcomes and uncovered no evidence of false-negative cases. We have demonstrated that blood spot GAGs analysis accurately discriminates between patients with confirmed MPS I and false-positive cases due to pseudodeficiency or heterozygosity and increases the specificity of newborn screening for MPS I.

scholarly journals Enhancing Newborn Screening for Tyrosinemia Type I

2008 ◽  
Vol 54 (4) ◽  
pp. 627-629 ◽  
Author(s):  
Kenneth A Pass ◽  
Mark Morrissey
Keyword(s):  
Newborn Screening ◽  
Type I ◽  
Tyrosinemia Type I
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