Search for


TEXT SIZE

search for



Measurement of Succinylacetone Using HPLC-Tandem Mass Spectrometry and Establishment of a Cut-off Value
J Lab Med Qual Assur 2018;40:149-154
Published online September 30, 2018
© 2018 Korean Association of External Quality Assessment Service.

Sun Hee Jun1,*, Jong Do Seo2,*, Kyunghoon Lee1,2, and Junghan Song1,2

1Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam; 2Department of Laboratory Medicine, Seoul NationalUniversity College of Medicine, Seoul, Korea
Correspondence to: Junghan Song
Department of Laboratory Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundanggu, Seongnam 13620, Korea
Tel: +82-31-787-7691
Fax: +82-31-787-4015
E-mail: Songjhcp@snu.ac.kr
*These authors contributed equally to this work.
Received April 11, 2018; Revised July 9, 2018; Accepted July 9, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Background: Newborn screening of tyrosinemia type 1 is important for identifying infants at risk for developing this disease before life-threatening symptoms occur. It is difficult to differentiate between tyrosinemia type 1 and transient neonatal tyrosinemia (TNT) by analyzing tyrosine alone. Thus, succinylacetone must be analyzed. In this study, we measured succinylacetone in dried blood spot (DBS) by HPLC-tandem mass spectrometry (HPLC-MS/MS) and established cut-off values.
Methods: We used the hydrazine derivatization method to measure succinylacetone in 127 DBSs showing normal results in the newborn screening test and 93 DBSs showing increased tyrosine levels. We established cut-off values using the 99.9th percentile value or median+5 standard deviation value.
Results: Succinylacetone levels determined by our method were well-correlated with the results recommended by the Centers for Disease Control and Prevention for proficiency testing (r =0.9968). The succinylacetone levels in normal newborn DBSs were significantly lower than those in DBSs with high tyrosine levels (P 竊0.001). The cut-off values were calculated to be 1.3 關M from the results of 127 normal DBS samples and 2.2 關M from 220 DBSs, including in 93 newborns with TNT.
Conclusions: Measurement of succinylacetone in DBSs by HPLC-MS/MS is useful in individuals with increased tyrosine concentrations and can be used for rapid differential diagnosis of tyrosinemia when an appropriate cut-off value is established.
Keywords : Succinylacetone, Tyrosinemias, Tandem mass spectrometry
References
  1. Mitchell GA, Grompe M, Lambert M, Tanguay RM. Hypertyrosinemia. In: Scriver CR, Beaudet AL, Sly WS, Valle DV, editors. The metabolic and molecular bases of inherited disease. 8th ed. New York (NY): McGraw-Hill, 2001:1777-805.
  2. Chinsky JM, Singh R, Ficicioglu C, van Karnebeek CDM, Grompe M, Mitchell G, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med 2017;19. https://doi.org/10.1038/gim.2017.101.
    CrossRef
  3. Berger R, van Faassen H, Smith GP. Biochemical studies on the enzymatic deficiencies in hereditary tyrosinemia. Clin Chim Acta 1983;134:129-41.
    CrossRef
  4. Kvittingen EA. Tyrosinaemia type I: an update. J Inherit Metab Dis 1991;14:554-62.
    Pubmed CrossRef
  5. Holme E, Lindstedt S. Nontransplant treatment of tyrosinemia. Clin Liver Dis 2000;4:805-14.
    CrossRef
  6. Grenier A, Lescault A, Laberge C, Gagne R, Mamer O. Detection of succinylacetone and the use of its measurement in mass screening for hereditary tyrosinemia. Clin Chim Acta 1982;123:93-9.
    CrossRef
  7. Jakobs C, Dorland L, Wikkerink B, Kok RM, de Jong AP, Wadman SK. Stable isotope dilution analysis of succinylacetone using electron capture negative ion mass fragmentography: an accurate approach to the pre- and neonatal diagnosis of hereditary tyrosinemia type I. Clin Chim Acta 1988;171:223-31.
    CrossRef
  8. La Marca G, Malvagia S, Pasquini E, Innocenti M, Fernandez MR, Donati MA, et al. The inclusion of succinylacetone as marker for tyrosinemia type I in expanded newborn screening programs. Rapid Commun Mass Spectrom 2008;22:812-8.
    Pubmed CrossRef
  9. Metz TF, Mechtler TP, Merk M, Gottschalk A, Lukacin R, Herkner KR, et al. Evaluation of a novel, commercially available mass spectrometry kit for newborn screening including succinylacetone without hydrazine. Clin Chim Acta 2012;413:1259-64.
    Pubmed CrossRef
  10. Clinical and Laboratory Standards Institute. Defining, establishing, and verifying reference intervals in the clinical laboratory: approved guideline: C28-A3C. 3rd ed. Wayne (PA): Clinical and Laboratory Standards Institute, 2010.
  11. Stinton C, Geppert J, Freeman K, Clarke A, Johnson S, Fraser H, et al. Newborn screening for Tyrosinemia type 1 using succinylacetone: a systematic review of test accuracy. Orphanet J Rare Dis 2017;12:48.
    Pubmed KoreaMed CrossRef