Abstract
Abnormal accumulation of very-long-chain fatty acids (VLCFAs), defined as molecules with greater than 22 carbons, and branched-chain fatty acids, pristanic and phytanic acids, is characteristic of inborn errors of peroxisomal biogenesis or function. X-linked adrenoleukodystrophy, Zellweger spectrum disorders, rhizomelic chondrodysplasia punctata, and Refsum syndrome can be diagnosed biochemically by quantitation of these metabolites in plasma. Ratios of C24/C22 and C26/C22 can help improve detection of X-linked adrenoleukodystrophy. Analysis using gas-chromatography mass spectrometry (GC/MS) after acid/base hydrolysis, organic solvent extraction, and derivatization is an established method for clinical diagnostics. This chapter describes detailed steps to process plasma samples for GC/MS analysis.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Nagotu S, Kalel VC, Erdmann R et al (2012) Molecular basis of peroxisomal biogenesis disorders caused by defects in peroxisomal matrix protein import. Biochim Biophys Acta 1822(9):1326–1336
De Biase I, Tortorelli S, Kratz L et al (2020) Laboratory diagnosis of disorders of peroxisomal biogenesis and function: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med 22(4):686–697
Hunt MC, Siponen MI, Alexson SE (2012) The emerging role of acyl-CoA thioesterases and acyltransferases in regulating peroxisomal lipid metabolism. Biochim Biophys Acta 1822(9):1397–1410
Wanders RJ, Duran M (2008) Very-long-chain fatty acids and phytanic acid. In: Blau N, Duran M, Gibson KM (eds) Laboratory guide to the methods in biochemical genetics. Springer, Berlin
Vreken P, van Lint AE, Bootsma AH et al (1998) Rapid stable isotope dilution analysis of very-long-chain fatty acids, pristanic acid and phytanic acid using gas chromatography-electron impact mass spectrometry. J Chromatogr B Biomed Sci Appl 713(2):281–287
Lam C, Wong D, Cederbaum S et al (2012) Peanut consumption increases levels of plasma very long chain fatty acids in humans. Mol Genet Metab 107(3):620–622
Theda C, Woody RC, Naidu S et al (1993) Increased very long chain fatty acids in patients on a ketogenic diet: a cause of diagnostic confusion. J Ped 122(5):724–726
Werner LB, Hellgren LI, Raff M et al (2011) Effect of dairy fat on plasma phytanic acid in healthy volunteers- a randomized controlled study. Lipids Health Dis. https://doi.org/10.1186/1476-511X-10-95
Armangue T, Orsini JJ, Takanohashi A et al (2017) Neonatal detection of Aicardi Goutieres syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots. Mol Genet Metab 122(3):134–139
Tise CG, Morales JA, Lee AS et al (2021) Aicardi-Goutieres syndrome may present with positive newborn screen for X-linked adrenoleukodystrophy. Am J Med Genet A. https://doi.org/10.1002/ajmg.a.62160
Moser AB, Krieter N, Bezman L et al (1999) Plasma very long chain fatty acids in 3,000 peroxisome disease patients and 29,000 controls. Ann Neurol 45(1):100–110
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Scott, A.I. (2022). Very-Long-Chain Fatty Acids Quantification by Gas-Chromatography Mass Spectrometry. In: Garg, U. (eds) Clinical Applications of Mass Spectrometry in Biomolecular Analysis. Methods in Molecular Biology, vol 2546. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2565-1_45
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2565-1_45
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2564-4
Online ISBN: 978-1-0716-2565-1
eBook Packages: Springer Protocols