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This Article Full Text Full Text (PDF) All Versions of this Article: clinchem.2005.059790v1 52/3/482    most recent Submit an electronic Letter to the Editor about this paper Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Sander, J. Articles by Das, A. M. Search for Related Content PubMed PubMed Citation Articles by Sander, J. Articles by Das, A. M. Related Collections Molecular Diagnostics and Genetics Pediatric Clinical Chemistry Endocrinology and Metabolism

Newborn Screening for Hepatorenal Tyrosinemia: Tandem Mass Spectrometric Quantification of Succinylacetone

¹ Screening Laboratory, Hannover, Germany.
² Department of General Paediatrics, University Children’s Hospital, University of Düsseldorf, Düsseldorf, Germany.
³ Department of Paediatrics, Klinikum am Steinenberg, Reutlingen, Germany.
⁴ Department of Paediatrics, Medizinische Hochschule, Hannover, Germany.

^aAddress correspondence to this author at: Screening Laboratory, Hannover, Postfach 911009, D-30430 Hannover, Germany. Fax 49-5108-9216319; e-mail j.sander{at}metabscreen.de.

Background: False-positive and false-negative results occur in current newborn-screening programs for hepatorenal tyrosinemia, which measure tyrosine concentrations in blood spots, sometimes in combination with other metabolites, including succinylacetone. We present our experience with a newly described method for succinylacetone quantification in routine newborn screening.

Methods: Succinylacetone was extracted from blood spots that had already been extracted with absolute methanol for acylcarnitine and amino acid analysis. The solvent was acetonitrile–water (80:20 by volume) containing formic acid, hydrazine hydrate, and 100 nmol/L 5,7-dioxooctanoic acid as internal standard. Analysis was performed by tandem mass spectrometry in a separate run.

Results: Of 61 344 samples, 99.6% had succinylacetone concentrations 5 µmol/L. With a cutoff of 10 µmol/L, no false-positive results were obtained. In 2 patients, the succinylacetone concentrations in the dried blood spots from the 36th and 56th hours of life were 152 and 271 µmol/L, respectively, and the tyrosine concentrations were 54 and 129 µmol/L. Hepatorenal tyrosinemia was subsequently confirmed in both patients. Retrospective analysis of the neonatal screening samples of 2 additional known patients revealed increased succinylacetone concentrations of 46 and 169 µmol/L, respectively.

Conclusions: Tandem mass spectrometric quantification directly from residual blood spots is a useful method for the early detection of hepatorenal tyrosinemia in newborn-screening programs.

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

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

				C. Turgeon, M. J. Magera, P. Allard, S. Tortorelli, D. Gavrilov, D. Oglesbee, K. Raymond, P. Rinaldo, and D. Matern Combined Newborn Screening for Succinylacetone, Amino Acids, and Acylcarnitines in Dried Blood Spots Clin. Chem., April 1, 2008; 54(4): 657 - 664. [Abstract] [Full Text] [PDF]