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1
University of Texas Southwestern Medical Center, Department of Pathology, and Children’s Medical Center of Dallas, TX 75235.
2
University of Colorado Health Science Center, Department
of Pediatrics, Denver, CO 80262.
3
University of Padua, Department of Pediatrics, I-35128
Padua, Italy.
4
Mayo Clinic, Department of Laboratory Medicine and
Pathology, Rochester, MN 55905.
a Address correspondence to this author at: Children’s Medical Center, Department of Pathology, 1935 Motor St., Dallas, TX 75235. Fax 214-456-6199; e-mail PJONES{at}CHILDMED.DALLAS.TX.US
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.
The following articles in journals at HighWire Press have cited this article:
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  P. M. Jones Clin. Chem., March 1, 2004; 50(3): 687 - 688. [Full Text] [PDF]
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B. Szponar, L. Krasnik, T. Hryniewiecki, A. Gamian, and L. Larsson Distribution of 3-Hydroxy Fatty Acids in Tissues after Intraperitoneal Injection of Endotoxin Clin. Chem., July 1, 2003; 49(7): 1149 - 1153. [Abstract] [Full Text] [PDF]
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P. M. Jones, S. Tjoa, P. V. Fennessey, S. I. Goodman, and M. J. Bennett Addition of Quantitative 3-Hydroxy-Octadecanoic Acid to the Stable Isotope Gas Chromatography-Mass Spectrometry Method for Measuring 3-Hydroxy Fatty Acids Clin. Chem., January 1, 2002; 48(1): 176 - 179. [Full Text] [PDF]
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L. Sweetman Newborn Screening by Tandem Mass Spectrometry: Gaining Experience Clin. Chem., November 1, 2001; 47(11): 1937 - 1938. [Full Text] [PDF]
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 S. L. Gray, K. J. Cummings, F. R. Jirik, and N. M. Sherwood Targeted Disruption of the Pituitary Adenylate Cyclase-Activating Polypeptide Gene Results in Early Postnatal Death Associated with Dysfunction of Lipid and Carbohydrate Metabolism Mol. Endocrinol., October 1, 2001; 15(10): 1739 - 1747. [Abstract] [Full Text] [PDF]
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P. M. Jones, M. Moffitt, D. Joseph, P. A. Harthcock, R. L. Boriack, J. A. Ibdah, A. W. Strauss, and M. J. Bennett Accumulation of Free 3-Hydroxy Fatty Acids in the Culture Media of Fibroblasts from Patients Deficient in Long-Chain L-3-Hydroxyacyl-CoA Dehydrogenase: A Useful Diagnostic Aid Clin. Chem., July 1, 2001; 47(7): 1190 - 1194. [Abstract] [Full Text] [PDF]
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