Improved stable isotope dilution-gas chromatography-mass spectrometry method for serum or plasma free 3-hydroxy-fatty acids and its utility for the study of disorders of mitochondrial fatty acid β-oxidation

Patricia M. Jones, Rebecca Quinn, Paul V. Fennessey, Susan Tjoa, Stephen I. Goodman, Stephany Fiore, Alberto B. Burlina, Piero Rinaldo, Richard L. Boriack, Michael J. Bennett

Research output: Contribution to journalArticle

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Abstract

Background: Disorders of fatty acid oxidation (FAO) are difficult to diagnose, primarily because in many of the FAO disorders measurable biochemical intermediates accumulate in body fluids only during acute illness. Increased concentrations of 3-hydroxy-fatty acids (3-OH-FAs) in the blood are indicative of FAO disorders of the long- and short-chain 3-hydroxy- acyl-CoA dehydrogenases, LCHAD and SCHAD. We describe a serum/plasma assay for the measurement of 3-OH-FAs with carbon chain lengths from C6 to C16. Methods: We used stable isotope dilution gas chromatography-mass spectrometry (GC-MS) with electron impact ionization and selected ion monitoring. Natural and isotope-labeled compounds were synthesized for the assay. Results: The assay was linear from 0.2 to 50 μmol/L for all six 3-OH-FAs. CVs were 5-15% at concentrations near the upper limits seen in healthy subjects. In 43 subjects, the medians (and ranges) in μmol/L were as follows: 3-OH-C6, 0.8 (0.3-2.2); 3-OH-C8, 0.4 (0.2-1.0); 3-OH-C10, 0.3 (0.2- 0.6); 3-OH-C12, 0.3 (0.2- 0.6); 3-OH-C14, 0.2 (0.0-0.4); and 3-OH-C16, 0.2 (0.0-0.5). 3- OH-FAs were increased in infants receiving formula containing medium chain triglycerides. Two patients diagnosed with LCHAD deficiency showed marked increases in 3-OH-C14 and 3-OH-C16 concentrations. Two patients diagnosed with SCHAD deficiency showed increased shorter chain 3-OH-FAs but no increases in 3-OH-C14 to 3-OH-C16. Conclusion: Measuring blood concentrations of the 3-OH-FAs with this assay may be a valuable tool for helping to rapidly identify deficiencies in LCHAD and SCHAD and may also provide useful information about the status of the FAO pathway. (C) 2000 American Association for Clinical Chemistry.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalClinical Chemistry
Volume46
Issue number2
StatePublished - 2000

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Mitochondrial Diseases
Hydroxy Acids
Isotopes
Gas chromatography
Gas Chromatography-Mass Spectrometry
Dilution
Mass spectrometry
Fatty Acids
Plasmas
Oxidation
Serum
Assays
hydroxide ion
Acyl-CoA Dehydrogenases
Blood
Impact ionization
Infant Formula
Body fluids
Body Fluids

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Improved stable isotope dilution-gas chromatography-mass spectrometry method for serum or plasma free 3-hydroxy-fatty acids and its utility for the study of disorders of mitochondrial fatty acid β-oxidation. / Jones, Patricia M.; Quinn, Rebecca; Fennessey, Paul V.; Tjoa, Susan; Goodman, Stephen I.; Fiore, Stephany; Burlina, Alberto B.; Rinaldo, Piero; Boriack, Richard L.; Bennett, Michael J.

In: Clinical Chemistry, Vol. 46, No. 2, 2000, p. 149-155.

Research output: Contribution to journalArticle

Jones, Patricia M. ; Quinn, Rebecca ; Fennessey, Paul V. ; Tjoa, Susan ; Goodman, Stephen I. ; Fiore, Stephany ; Burlina, Alberto B. ; Rinaldo, Piero ; Boriack, Richard L. ; Bennett, Michael J. / Improved stable isotope dilution-gas chromatography-mass spectrometry method for serum or plasma free 3-hydroxy-fatty acids and its utility for the study of disorders of mitochondrial fatty acid β-oxidation. In: Clinical Chemistry. 2000 ; Vol. 46, No. 2. pp. 149-155.
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abstract = "Background: Disorders of fatty acid oxidation (FAO) are difficult to diagnose, primarily because in many of the FAO disorders measurable biochemical intermediates accumulate in body fluids only during acute illness. Increased concentrations of 3-hydroxy-fatty acids (3-OH-FAs) in the blood are indicative of FAO disorders of the long- and short-chain 3-hydroxy- acyl-CoA dehydrogenases, LCHAD and SCHAD. We describe a serum/plasma assay for the measurement of 3-OH-FAs with carbon chain lengths from C6 to C16. Methods: We used stable isotope dilution gas chromatography-mass spectrometry (GC-MS) with electron impact ionization and selected ion monitoring. Natural and isotope-labeled compounds were synthesized for the assay. Results: The assay was linear from 0.2 to 50 μmol/L for all six 3-OH-FAs. CVs were 5-15{\%} at concentrations near the upper limits seen in healthy subjects. In 43 subjects, the medians (and ranges) in μmol/L were as follows: 3-OH-C6, 0.8 (0.3-2.2); 3-OH-C8, 0.4 (0.2-1.0); 3-OH-C10, 0.3 (0.2- 0.6); 3-OH-C12, 0.3 (0.2- 0.6); 3-OH-C14, 0.2 (0.0-0.4); and 3-OH-C16, 0.2 (0.0-0.5). 3- OH-FAs were increased in infants receiving formula containing medium chain triglycerides. Two patients diagnosed with LCHAD deficiency showed marked increases in 3-OH-C14 and 3-OH-C16 concentrations. Two patients diagnosed with SCHAD deficiency showed increased shorter chain 3-OH-FAs but no increases in 3-OH-C14 to 3-OH-C16. Conclusion: Measuring blood concentrations of the 3-OH-FAs with this assay may be a valuable tool for helping to rapidly identify deficiencies in LCHAD and SCHAD and may also provide useful information about the status of the FAO pathway. (C) 2000 American Association for Clinical Chemistry.",
author = "Jones, {Patricia M.} and Rebecca Quinn and Fennessey, {Paul V.} and Susan Tjoa and Goodman, {Stephen I.} and Stephany Fiore and Burlina, {Alberto B.} and Piero Rinaldo and Boriack, {Richard L.} and Bennett, {Michael J.}",
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T1 - Improved stable isotope dilution-gas chromatography-mass spectrometry method for serum or plasma free 3-hydroxy-fatty acids and its utility for the study of disorders of mitochondrial fatty acid β-oxidation

AU - Jones, Patricia M.

AU - Quinn, Rebecca

AU - Fennessey, Paul V.

AU - Tjoa, Susan

AU - Goodman, Stephen I.

AU - Fiore, Stephany

AU - Burlina, Alberto B.

AU - Rinaldo, Piero

AU - Boriack, Richard L.

AU - Bennett, Michael J.

PY - 2000

Y1 - 2000

N2 - Background: Disorders of fatty acid oxidation (FAO) are difficult to diagnose, primarily because in many of the FAO disorders measurable biochemical intermediates accumulate in body fluids only during acute illness. Increased concentrations of 3-hydroxy-fatty acids (3-OH-FAs) in the blood are indicative of FAO disorders of the long- and short-chain 3-hydroxy- acyl-CoA dehydrogenases, LCHAD and SCHAD. We describe a serum/plasma assay for the measurement of 3-OH-FAs with carbon chain lengths from C6 to C16. Methods: We used stable isotope dilution gas chromatography-mass spectrometry (GC-MS) with electron impact ionization and selected ion monitoring. Natural and isotope-labeled compounds were synthesized for the assay. Results: The assay was linear from 0.2 to 50 μmol/L for all six 3-OH-FAs. CVs were 5-15% at concentrations near the upper limits seen in healthy subjects. In 43 subjects, the medians (and ranges) in μmol/L were as follows: 3-OH-C6, 0.8 (0.3-2.2); 3-OH-C8, 0.4 (0.2-1.0); 3-OH-C10, 0.3 (0.2- 0.6); 3-OH-C12, 0.3 (0.2- 0.6); 3-OH-C14, 0.2 (0.0-0.4); and 3-OH-C16, 0.2 (0.0-0.5). 3- OH-FAs were increased in infants receiving formula containing medium chain triglycerides. Two patients diagnosed with LCHAD deficiency showed marked increases in 3-OH-C14 and 3-OH-C16 concentrations. Two patients diagnosed with SCHAD deficiency showed increased shorter chain 3-OH-FAs but no increases in 3-OH-C14 to 3-OH-C16. Conclusion: Measuring blood concentrations of the 3-OH-FAs with this assay may be a valuable tool for helping to rapidly identify deficiencies in LCHAD and SCHAD and may also provide useful information about the status of the FAO pathway. (C) 2000 American Association for Clinical Chemistry.

AB - Background: Disorders of fatty acid oxidation (FAO) are difficult to diagnose, primarily because in many of the FAO disorders measurable biochemical intermediates accumulate in body fluids only during acute illness. Increased concentrations of 3-hydroxy-fatty acids (3-OH-FAs) in the blood are indicative of FAO disorders of the long- and short-chain 3-hydroxy- acyl-CoA dehydrogenases, LCHAD and SCHAD. We describe a serum/plasma assay for the measurement of 3-OH-FAs with carbon chain lengths from C6 to C16. Methods: We used stable isotope dilution gas chromatography-mass spectrometry (GC-MS) with electron impact ionization and selected ion monitoring. Natural and isotope-labeled compounds were synthesized for the assay. Results: The assay was linear from 0.2 to 50 μmol/L for all six 3-OH-FAs. CVs were 5-15% at concentrations near the upper limits seen in healthy subjects. In 43 subjects, the medians (and ranges) in μmol/L were as follows: 3-OH-C6, 0.8 (0.3-2.2); 3-OH-C8, 0.4 (0.2-1.0); 3-OH-C10, 0.3 (0.2- 0.6); 3-OH-C12, 0.3 (0.2- 0.6); 3-OH-C14, 0.2 (0.0-0.4); and 3-OH-C16, 0.2 (0.0-0.5). 3- OH-FAs were increased in infants receiving formula containing medium chain triglycerides. Two patients diagnosed with LCHAD deficiency showed marked increases in 3-OH-C14 and 3-OH-C16 concentrations. Two patients diagnosed with SCHAD deficiency showed increased shorter chain 3-OH-FAs but no increases in 3-OH-C14 to 3-OH-C16. Conclusion: Measuring blood concentrations of the 3-OH-FAs with this assay may be a valuable tool for helping to rapidly identify deficiencies in LCHAD and SCHAD and may also provide useful information about the status of the FAO pathway. (C) 2000 American Association for Clinical Chemistry.

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