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Clinical Chemistry 54: 657-664, 2008. First published February 15, 2008; 10.1373/clinchem.2007.101949
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Right arrow Pediatric Clinical Chemistry
(Clinical Chemistry. 2008;54:657-664.)
© 2008 American Association for Clinical Chemistry, Inc.

Pediatric Clinical Chemistry

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

Coleman Turgeon1, Mark J. Magera1, Pierre Allard2, Silvia Tortorelli1, Dimitar Gavrilov1, Devin Oglesbee1, Kimiyo Raymond1, Piero Rinaldo1 and Dietrich Matern1,a

1 Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, MN; 2 Biochemical Genetics Laboratory, Hôpital St. Justine, Montreal, Canada.

aAddress correspondence to this author at: Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905; Fax (507) 266-2888; e-mail matern{at}mayo.edu.

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.




The following articles in journals at HighWire Press have cited this article:


Home page
 Clin. Chem.Home page
K. A. Pass and M. Morrissey
Enhancing Newborn Screening for Tyrosinemia Type I
Clin. Chem., April 1, 2008; 54(4): 627 - 629.
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