Article

Editorial

Ann Lab Med 2023; 43(2): 133-134

Published online March 1, 2023 https://doi.org/10.3343/alm.2023.43.2.133

Copyright © Korean Society for Laboratory Medicine.

Non-derivatizing Tandem Mass Spectrometry Assay for Expanded Newborn Screening and Cutoffs for Preterm Neonates

Joon Hee Lee, M.D.1,2 and Junghan Song, M.D., Ph.D.1,2

1Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 2Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Junghan Song, M.D., Ph.D.
Department of Laboratory Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 beon-gil, Bundang-du, Seongnam 13620, Korea
Tel: +82-31-787-7691, Fax: +82-31-787-4015, E-mail: songjhcp@snu.ac.kr

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been increasingly utilized in clinical laboratory testing through adequate method development and operation [1, 2]. Based on tandem mass spectrometry (MS/MS) analysis of amino acids and acylcarnitines in newborn dried blood spots, extended newborn screening for amino acid disorders, fatty acid oxidation defects, and some organic acidemias has been successfully implemented worldwide [3, 4]. In early newborn screening, dried blood spots were derivatized by butyl esterification and subsequently tested by MS/MS using the 102 neutral loss scan and 85 precursor ion scan methods. Due to drawbacks of the derivatization method, including the handling of hazardous reagents and a relatively complex and long sample preparation process, non-derivatization techniques for selected amino acid and acylcarnitine tests have been introduced. Initially, all laboratories that conducted MS/MS newborn screening tests used in-house developed tests, including derivatization as well as non-derivatization tests. However, since the introduction of specialized commercial kits, such as the NeoBase kit (PerkinElmer Finland, Turku, Finland), MassChrom (Chromsystems, Munich, Germany), and NeoMass AAAC (Labsystems Diagnostics, Vantaa, Finland), all of which are for non-derivatization tests, many laboratories use commercial kits for MS/MS newborn screening. Recently, PerkinElmer Finland launched the NeoBase 2 Non-derivatized MSMS kit, which can additionally analyze adenosine for adenosine deaminase deficiency, very-long-chain acylcarnitines and lysophosphatidylcholines (LPC) for X-linked adrenoleukodystrophy, and succinylacetone for second-tier differential diagnosis of tyrosinemia type 1 and transient tyrosinemia of the newborn.

It is crucial to use appropriate cutoffs for preterm babies for accurate result interpretation and to minimize false negatives without generating an excessive number of false positives. Zytkovicz, et al. [5] pointed out that different cutoffs need to be established for different subpopulations of newborns, including full-term, premature or low birth weight, very low birth weight, very low birth weight on total parenteral nutrition, and different specimen collection ages.

In this issue, Lee, et al. [6] comprehensively evaluated the analytical performance of the NeoBase 2 kit. The authors found that it showed adequate analytical performance in terms of precision, concordance with their in-house derivatization-based assay, limit of detection, lower limit of quantification, linearity, recoveries, and carryover. Tyrosinemia type 1 and transient tyrosinemia of the newborn were successfully differentiated by measuring succinylacetone. The authors also evaluated different cutoffs in preterm neonates in the Korean population. They identified 15 analytes (arginine, citrulline, tyrosine, adenosine, C0, C2, C4, C5, C6DC, C8:1, C12:1, C14:1, C16, C18:2, and C20:0- LPCs) showing different cutoffs between preterm and term babies and proposed higher preterm cutoffs for three analytes (tyrosine, adenosine, and C20:0-LPC) for the first time in Korea.

This study will be of help to readers interested in MS/MS-based special chemistry tests, especially, those affiliated to laboratories that conduct extended newborn screening using MS/MS. The authors proposed different cutoffs for preterm neonates, which is helpful for the accurate interpretation of newborn screening tests to minimize false negatives without generating an excessive number of false positives.

Lee JH and Song J contributed to manuscript writing and approved the submission of the final manuscript.

  1. Rappold BA. Review of the use of liquid chromatography-tandem mass spectrometry in clinical laboratories: Part I-Development. Ann Lab Med 2022;42:121-40.
    Pubmed KoreaMed CrossRef
  2. Rappold BA. Review of the use of liquid chromatography-tandem mass spectrometry in clinical laboratories: Part II-Operations. Ann Lab Med 2022;42:531-57.
    Pubmed KoreaMed CrossRef
  3. Chace DH, Kalas TA, Naylor EW. The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genomics Hum Genet 2002;3:17-45.
    Pubmed CrossRef
  4. Wilcken B, Wiley V, Hammond J, Carpenter K. Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N Engl J Med 2003;348:2304-12.
    Pubmed CrossRef
  5. Zytkovicz TH, Fitzgerald EF, Marsden D, Larson CA, Shih VE, Johnson DM, et al. Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. Clin Chem 2001;47:1945-55.
    Pubmed CrossRef
  6. Lee B, Heo WY, Kim JA, Lee HS, Hwang N, Park HD, et al. Comprehensive evaluation of the NeoBase 2 non-derivatized MSMS assay with exploration of analytes with significantly different levels between term and preterm neonates. Ann Lab Med 2023;43:153-66.
    Pubmed CrossRef