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Targeted ultra performance liquid chromatography tandem mass spectrometry procedures for the diagnosis of inborn errors of metabolism: validation through ERNDIM external quality assessment schemes

  • Clara Oliva , Angela Arias , Pedro Ruiz-Sala , Judit Garcia-Villoria , Rachel Carling ORCID logo , Jörgen Bierau , George J. G. Ruijter , Mercedes Casado , Aida Ormazabal and Rafael Artuch EMAIL logo
Published/Copyright: March 11, 2024
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 10

Abstract

Objectives

Early diagnosis of inborn errors of metabolism (IEM) is crucial to ensure early detection of conditions which are treatable. This study reports on targeted metabolomic procedures for the diagnosis of IEM of amino acids, acylcarnitines, creatine/guanidinoacetate, purines/pyrimidines and oligosaccharides, and describes its validation through external quality assessment schemes (EQA).

Methods

Analysis was performed on a Waters ACQUITY UPLC H-class system coupled to a Waters Xevo triple-quadrupole (TQD) mass spectrometer, operating in both positive and negative electrospray ionization mode. Chromatographic separation was performed on a CORTECS C18 column (2.1 × 150, 1.6 µm). Data were collected by multiple reaction monitoring.

Results

The internal and EQA results were generally adequate, with a few exceptions. We calculated the relative measurement error (RME) and only a few metabolites displayed a RME higher than 30 % (asparagine and some acylcarnitine species). For oligosaccharides, semi-quantitative analysis of an educational panel clearly identified the 8 different diseases included.

Conclusions

Overall, we have validated our analytical system through an external quality control assessment. This validation will contribute to harmonization between laboratories, thus improving identification and management of patients with IEM.

Keywords: inborn errors of metabolism; UPLC; tandem mass spectrometry; targeted metabolomics; external quality assessment
Corresponding author: Rafael Artuch, Clinical Biochemistry Department, Institut de Recerca Sant Joan de Déu, Barcelona, Passeig Sant Joan de Déu, 2, Esplugues de Llobregat, 08950, Barcelona, Spain; and Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain, Phone: +34932806169, E-mail:

Acknowledgments

ERNDIM (European Research Network for evaluation and improvement of screening, diagnosis and treatment of Inherited Disorders of Metabolism. www.erndim.org) is an independent not-for-profit foundation which provides External Quality Assurance schemes in the field of inborn errors of metabolis.

  1. Research ethics: The study was conducted following the Helsinki Declaration of 1975 as revised in 2013. The Ethical Committee of the Hospital Sant Joan de Déu approved the study. For oligosaccharides analysis, samples are anonymous and informed consents were collected by the Hospitals donating the samples.

  2. Informed consent: For oligosaccharides analysis, samples are anonymous and informed consents were collected by the Hospitals donating the samples.

  3. Author contributions: Clara Oliva: Methodology, Investigation, Formal analysis. Writing original draft. Angela Arias: Methodology, Investigation, Formal analysis. Writing original draft. Pedro Ruiz-Sala: Writing – review & editing. Formal analysis Judit Garcia-Villoria: Writing – review & editing. Formal analysis. Rachel Carling: Writing – review & editing. Formal analysis. Jörgen Bierau: Writing – review & editing. Formal analysis. George J.G. Ruijter: Writing – review & editing. Conceptualization, Supervision. Mercedes Casado: Methodology, Investigation, Formal analysis. Aida Ormazabal: Methodology, Investigation, Formal analysis. Rafael Artuch: Conceptualization, Supervision. Funding acquisition. Writing – review & editing. The authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

  5. Research funding: This work was supported by the Instituto de Salud Carlos III (PI20-00340) (co-funded by European Regional Development Fund “A way to make Europe”); the Center for Biomedical Research on Rare Diseases (CIBERER); and Carmen de Torres grants (Institut de Recerca Sant Joan de Déu). The Department of Clinical Biochemistry is part of the ‘Centre Daniel Bravo de Diagnòstic i Recerca en Malalties Minoritàries’.

  6. Data availability: Original data about external quality assessment results are available in Supplementary Table 4. Data will be available on reasonably request.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2023-1291).

Received: 2023-11-14
Accepted: 2024-02-22
Published Online: 2024-03-11
Published in Print: 2024-09-25

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2023-1291
Keywords for this article
inborn errors of metabolism; UPLC; tandem mass spectrometry; targeted metabolomics; external quality assessment

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Six years of progress – highlights from the IFCC Emerging Technologies Division
  4. IFCC Papers
  5. Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research
  6. Bilirubin measurements in neonates: uniform neonatal treatment can only be achieved by improved standardization
  7. Validation and verification framework and data integration of biosensors and in vitro diagnostic devices: a position statement of the IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MBHLM) and the IFCC Scientific Division
  8. Linearity assessment: deviation from linearity and residual of linear regression approaches
  9. HTA model for laboratory medicine technologies: overview of approaches adopted in some international agencies
  10. Considerations for applying emerging technologies in paediatric laboratory medicine
  11. A global perspective on the status of clinical metabolomics in laboratory medicine – a survey by the IFCC metabolomics working group
  12. The LEAP checklist for laboratory evaluation and analytical performance characteristics reporting of clinical measurement procedures
  13. General Clinical Chemistry and Laboratory Medicine
  14. Assessing post-analytical phase harmonization in European laboratories: a survey promoted by the EFLM Working Group on Harmonization
  15. Potential medical impact of unrecognized in vitro hypokalemia due to hemolysis: a case series
  16. Quantification of circulating alpha-1-antitrypsin polymers associated with different SERPINA1 genotypes
  17. Targeted ultra performance liquid chromatography tandem mass spectrometry procedures for the diagnosis of inborn errors of metabolism: validation through ERNDIM external quality assessment schemes
  18. Improving protocols for α-synuclein seed amplification assays: analysis of preanalytical and analytical variables and identification of candidate parameters for seed quantification
  19. Evaluation of analytical performance of AQUIOS CL flow cytometer and method comparison with bead-based flow cytometry methods
  20. IgG and kappa free light chain CSF/serum indices: evaluating intrathecal immunoglobulin production in HIV infection in comparison with multiple sclerosis
  21. Reference Values and Biological Variations
  22. Reference intervals of circulating secretoneurin concentrations determined in a large cohort of community dwellers: the HUNT study
  23. Sharing reference intervals and monitoring patients across laboratories – findings from a likely commutable external quality assurance program
  24. Verification of bile acid determination method and establishing reference intervals for biochemical and haematological parameters in third-trimester pregnant women
  25. Confounding factors of the expression of mTBI biomarkers, S100B, GFAP and UCH-L1 in an aging population
  26. Cancer Diagnostics
  27. Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA
  28. Diabetes
  29. Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods
  30. Letters to the Editor
  31. Are there any reasons to use three levels of quality control materials instead of two and if so, what are the arguments?
  32. Issues for standardization of neonatal bilirubinemia: a case of delayed phototherapy initiation
  33. The routine coagulation assays plasma stability – in the wake of the new European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) biological variability database
  34. Improving HCV diagnosis following a false-negative anti-HCV result
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