Abstract
Urine organic acid analysis has been a cornerstone of the laboratory diagnosis of inborn errors of metabolism for decades. Gas chromatography-mass spectrometry (GC-MS) allows the identification and quantification of a range of analytes that can be diagnostic and used to monitor patients throughout their treatment. Simply described, organic acids are extracted into an organic solvent via liquid/liquid extraction, dried and derivatized. After sample preparation is complete, analysis is most commonly performed by GC-MS to identify and quantify relevant compounds. The overall profile is then interpreted by a biochemical geneticist, who looks for patterns associated with specific disorders. Organic acid analysis can identify those disorders thought of as classical organic acidurias, such as methylmalonic aciduria, isovaleric aciduria, and propionic aciduria, as well as ever-increasing numbers of amino acidopathies, fatty acid oxidation disorders, and mitochondrial diseases. Analysis of organic acid profiles is challenging and must be performed by both qualified laboratory technologists and laboratory directors.
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Abbreviations
- 2OHGA:
-
2-Hydroxyglutaric acid
- 3OHGA:
-
3-Hydroxyglutaric acid
- BSTFA + TMCS:
-
N,O-Bis(trimethylsilyl)trifluoroacetamide
- GC-MS:
-
Gas chromatography-mass spectrometry
- IVA:
-
Isovaleric acidemia
- MMA:
-
Methylmalonic acidemia
- PA:
-
Propionic acidemia
- PDA:
-
Pentadecanoic acid
- UOA:
-
Urine organic acid analysis
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Acknowledgment
The authors would like to acknowledge Dr. Piero Rinaldo [9] for his permission to reference and use materials from his previous version of this chapter and for his comprehensive training in organic acid analysis.
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Hall, P.L., Tortorelli, S. (2024). Organic Acids. In: Blau, N., Vaz, F.M. (eds) Laboratory Guide to the Methods in Biochemical Genetics. Springer, Cham. https://doi.org/10.1007/978-3-031-58819-8_5
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