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One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

One-step Metabolomics: Carbohydrates, Organic and Amino Acids Quantified in a Single Procedure

Published on: June 25, 2010

Identification of potential interferents of methylmalonic acid: A previously unrecognized pitfall in clinical

Péter Monostori¹, Markus Godejohann², Joachim Janda³

¹Metabolic and Newborn Screening Laboratory, Department of Pediatrics, University of Szeged, Korányi fasor 14-15, Szeged H-6720, Hungary.

Clinical Biochemistry

|October 6, 2022

Abstract

Objectives:

Determination of methylmalonic acid (MMA) from dried blood spots (DBS) is commonly performed in clinical diagnostics and newborn screening for propionic acidemia (PA) and methylmalonic acidemia. Isobaric compounds of MMA having the same mass can affect diagnostic reliability and quantitative results, which represents a previously unrecognized pitfall in clinical assays for MMA. We set out to identify interfering substances of MMA in DBS, serum and urine samples from confirmed patients with PA and methylmalonic acidemia.

Methods:

Techniques included quadrupole time-of-flight high-resolution mass spectrometry (QTOF HR-MS), nuclear magnetic resonance (NMR) spectroscopy, liquid chromatography (LC) and tandem mass spectrometry (MS/MS).

Results:

The five isobaric metabolites detected in DBS, serum and urine from PA and methylmalonic acidemia patients were confirmed as 2-methyl-3-hydroxybutyrate, 3-hydroxyisovalerate, 2-hydroxyisovalerate, 3-hydroxyvalerate and succinate using a series of experiments. An additional unknown substance with low abundance remained unidentified.

Conclusions:

The presented results facilitate the diagnostic and quantitative reliability of the MMA determination in clinical assays. Isobaric species should be investigated in assays for MMA to eliminate possible interference in a wide range of conditions including PA, methylmalonic acidemia, a vitamin B₁₂ deficiency, ketosis and lactic acidosis.

Keywords:

Diagnostic reliability Interfering substance Mass spectrometry Metabolic disorder Methylmalonic acid Newborn screening

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