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Journal article

Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone

Sander J, Janzen N, Peter M, Sander S, Steuerwald U, Holtkamp U, Schwahn B, Mayatepek E, Trefz F, Das A...(+10 more)

Clinical Chemistry, vol. 52, issue 3 (2006) pp. 482-487

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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 < or =5 micromol/L. With a cutoff of 10 micromol/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 micromol/L, respectively, and the tyrosine concentrations were 54 and 129 micromol/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 micromol/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.

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