Abstract
Introduction
To explore the value of high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) in the follow-up for treatment of children with methylmalonic aciduria (MMA).
Methods
Methylmalonic acid (MMA), 2-methylcitric acid (MCA) and homocysteine (Hcy) were detected by LC–MS/MS in a total of 1016 samples whose estimated 0.5th and 99.5th percentiles was taken as the reference value. The samples of children with MMA and propionic aciduria (PA) who were followed up in our hospital from January 2017 to August 2018 were collected. Samples of dried blood spots, serum, and urine were taken from each patient on the same day. The concentration of the C3 indicator in the dried blood spots was tested by MS/MS. MMA, MCA, and Hcy in the dried blood spots were quantitatively determined by LC–MS/MS, the concentrations of MMA and MCA in urine filter papers were determined by gas chromatography–mass spectrometry (GC/MS), and the concentration of homocysteine in serum was determined by enzymatic cycling assay.
Results
Reference values of MMA, MCA and HCY by LC–MS/MS in the newborn population were determined. The samples from a total of 50 patients were collected, 48 were from children with MMA, and 2 were from children with PA. The first-order equation regression coefficient of MMA in the blood spots and MMA in urine was significant (P < 0.05), r2 = 0.736; the first-order equation regression coefficient of MCA in bthe lood spots and MCA in urine was significant (P < 0.05), r2 = 0.946; the first-order equation regression coefficient of tHcy in bthe lood spots and Hcy in serum was significant (P < 0.05), r2 = 0.771.
Conclusion
LC–MS/MS can be used for the follow-up of children with MMA after treatment, but it is necessary to establish a reference interval suitable for the local population.
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Acknowledgements
Funding
No funding or sponsorship was received for this study or publication of this article. The article processing charges were funded by the authors.
Authorship
All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.
Authorship Contributions
WYY and SY conceptualized and designed the study; WYY led the review process, drafted the initial manuscript and extracted data, and SY reviewed all articles; and JT analyzed and interpreted the data. All authors made substantial contributions to revising the manuscript. JT is responsible for the overall content. All authors read and approved the final manuscript.
Disclosures
Yanyun Wang, Yun Sun and Tao Jiang have nothing to disclose.
Compliance with Ethics Guidelines
This project received ethical approval from the Nanjing Maternity and Child Health Care Hospital for data and information. All procedures performed in studies involving human participants were in accordance with Nanjing Maternity and Child Health Care Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The parents of the study participants signed a written informed consent form to participate in this study.
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Wang, Y., Sun, Y. & Jiang, T. Clinical Application of LC–MS/MS in the Follow-Up for Treatment of Children with Methylmalonic Aciduria. Adv Ther 36, 1304–1313 (2019). https://doi.org/10.1007/s12325-019-00955-0
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DOI: https://doi.org/10.1007/s12325-019-00955-0