Startseite The markers of the organic acidemias and their ratios in healthy neonates in Serbian population
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The markers of the organic acidemias and their ratios in healthy neonates in Serbian population

  • Anđelo Beletić ORCID logo EMAIL logo , Aleksandra Tijanić , Petr Chrastina , Tatjana Nikolić , Aleksandar Stefanović und Sanja Stanković
Veröffentlicht/Copyright: 7. März 2022
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Drug Metabolism and Personalized Therapy
Aus der Zeitschrift Drug Metabolism and Personalized Therapy Band 37 Heft 3

Abstract

Objectives

The newborn screening (NBS) program in the Republic of Serbia has several decades of tradition, but it has not included any organic acidemias (OA). Therefore, this study aimed to establish the cut-offs of the corresponding NBS markers in the population of healthy newborns.

Methods

In dried blood samples (DBS) collected from 1,771 healthy newborns, we analyzed levels of propionylcarnitine (C3), isovalerylcarnitine (C5), and glutarylcarnitine (C5DC) using tandem mass spectrometry. Further we calculated the following ratios: C3/acetylcarnitine (C3/C2), C3/palmitoylcarnitine (C3/C16), C5/ free carnitine (C0), C5/C2, C5/C3, C5DC/octanoylcarnitine (C8), and C5DC/C0.

Results

The cut-offs for methylmalonic acidemia (MMA) or propionic acidemia (PA) were C3>5.73 μmol/L, C3/C2>0.23, and C3/C16>2.36. Based on the study findings, the screening results indicative for isovaleric acidemia (IVA) would include C5>0.372 μmol/L, C5/C0>0.020, C5/C2>0.019, and C5/C3>0.31. Finally, C5DC>0.303 μmol/L, C5DC/C8>7.1, and C5DC/C0>0.019 would justify further testing for glutaric acidemia type I (GA1). The cut-offs were satisfactorily validated via the comparison with worldwide estimates and data for several Caucasian populations.

Conclusions

The levels of the OA biomarkers in the Serbian population of healthy newborns have a distribution pattern similar to the other world populations. Therefore, the proposed cut-offs represent a reliable starting point for the future development of the OA NBS.

Keywords: cut-off; newborn screening (NBS); organic acidemias (OA); Serbia; tandem mass spectrometry
Corresponding author: Anđelo Beletić, PhD, Center for Medical Biochemistry, University Clinical Center of Serbia, Belgrade, Serbia, Phone: +381 60 1511083, E-mail:

  1. Research funding: Not applicable.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained for all individuals included in this study.

  5. Ethical approval: Ethics Committee of Clinical Center of Serbia approved the study (Permission No. 747/33/19.07.2018) and mother of each newborn signed the informed consent.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/dmpt-2021-0218).

Received: 2021-11-19
Accepted: 2022-02-08
Published Online: 2022-03-07

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/dmpt-2021-0218
Schlagwörter für diesen Artikel
cut-off; newborn screening (NBS); organic acidemias (OA); Serbia; tandem mass spectrometry

Artikel in diesem Heft

  1. Frontmatter
  2. Reviews
  3. Genotype-based chemotherapy for patients with gastrointestinal tumors: focus on oxaliplatin, irinotecan, and fluoropyrimidines
  4. Factors influencing methotrexate and methotrexate polyglutamate in patients with rheumatoid arthritis: a systematic review of population pharmacokinetics
  5. Original Articles
  6. Predicting drug–drug interactions by electrochemically driven cytochrome P450 3A4 reactions
  7. Evaluation of the stability of furosemide in tablet form during six-month storage in spaceflight and peculiarities of its pharmacokinetics and pharmacodynamics under conditions of anti-orthostatic hypokinesia
  8. CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers
  9. The markers of the organic acidemias and their ratios in healthy neonates in Serbian population
  10. Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling
  11. The efficacy of topical Marham-e-Akbar in chronic atopic dermatitis – an open-label interventional study
  12. In vitro metabolic biomodulation of irinotecan to increase potency and reduce dose-limiting toxicity by inhibition of SN-38 glucuronide formation
  13. Datura stramonium abrogates depression- and anxiety-like disorders in mice: possible involvement of monoaminergic pathways in its antidepressant activity
  14. Synergistic anti-cancer effects of Nigella sativa seed oil and conventional cytotoxic agent against human breast cancer
  15. Short Communication
  16. MTHFR c.665C>T guided fluoropyrimidine therapy in cancer: gender-dependent effect on dose requirements
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