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Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone.
Clin Chem 2006; 52(3):482-7CC

Abstract

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.

Authors+Show Affiliations

Screening Laboratory, Hannover, Germany. j.sander@metabscreen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

16439608

Citation

Sander, Johannes, et al. "Newborn Screening for Hepatorenal Tyrosinemia: Tandem Mass Spectrometric Quantification of Succinylacetone." Clinical Chemistry, vol. 52, no. 3, 2006, pp. 482-7.
Sander J, Janzen N, Peter M, et al. Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone. Clin Chem. 2006;52(3):482-7.
Sander, J., Janzen, N., Peter, M., Sander, S., Steuerwald, U., Holtkamp, U., ... Das, A. M. (2006). Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone. Clinical Chemistry, 52(3), pp. 482-7.
Sander J, et al. Newborn Screening for Hepatorenal Tyrosinemia: Tandem Mass Spectrometric Quantification of Succinylacetone. Clin Chem. 2006;52(3):482-7. PubMed PMID: 16439608.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Newborn screening for hepatorenal tyrosinemia: Tandem mass spectrometric quantification of succinylacetone. AU - Sander,Johannes, AU - Janzen,Nils, AU - Peter,Michael, AU - Sander,Stefanie, AU - Steuerwald,Ulrike, AU - Holtkamp,Ute, AU - Schwahn,Bernd, AU - Mayatepek,Ertan, AU - Trefz,Friedrich K, AU - Das,Anibh M, Y1 - 2006/01/26/ PY - 2006/1/28/pubmed PY - 2006/4/14/medline PY - 2006/1/28/entrez SP - 482 EP - 7 JF - Clinical chemistry JO - Clin. Chem. VL - 52 IS - 3 N2 - 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. SN - 0009-9147 UR - https://www.unboundmedicine.com/medline/citation/16439608/Newborn_screening_for_hepatorenal_tyrosinemia:_Tandem_mass_spectrometric_quantification_of_succinylacetone_ L2 - http://www.clinchem.org/cgi/pmidlookup?view=long&amp;pmid=16439608 DB - PRIME DP - Unbound Medicine ER -