Effects of fasting, feeding and exercise on plasma acylcarnitines among subjects with CPT2D, VLCADD and LCHADD/TFPD

Mol Genet Metab. 2020 Sep-Oct;131(1-2):90-97. doi: 10.1016/j.ymgme.2020.09.001. Epub 2020 Sep 6.

Abstract

Background: The plasma acylcarnitine profile is frequently used as a biochemical assessment for follow-up in diagnosed patients with fatty acid oxidation disorders (FAODs). Disease specific acylcarnitine species are elevated during metabolic decompensation but there is clinical and biochemical heterogeneity among patients and limited data on the utility of an acylcarnitine profile for routine clinical monitoring.

Methods: We evaluated plasma acylcarnitine profiles from 30 diagnosed patients with long-chain FAODs (carnitine palmitoyltransferase-2 (CPT2), very long-chain acyl-CoA dehydrogenase (VLCAD), and long-chain 3-hydroxy acyl-CoA dehydrogenase or mitochondrial trifunctional protein (LCHAD/TFP) deficiencies) collected after an overnight fast, after feeding a controlled low-fat diet, and before and after moderate exercise. Our purpose was to describe the variability in this biomarker and how various physiologic states effect the acylcarnitine concentrations in circulation.

Results: Disease specific acylcarnitine species were higher after an overnight fast and decreased by approximately 60% two hours after a controlled breakfast meal. Moderate-intensity exercise increased the acylcarnitine species but it varied by diagnosis. When analyzed for a genotype/phenotype correlation, the presence of the common LCHADD mutation (c.1528G > C) was associated with higher levels of 3-hydroxyacylcarnitines than in patients with other mutations.

Conclusions: We found that feeding consistently suppressed and that moderate intensity exercise increased disease specific acylcarnitine species, but the response to exercise was highly variable across subjects and diagnoses. The clinical utility of routine plasma acylcarnitine analysis for outpatient treatment monitoring remains questionable; however, if acylcarnitine profiles are measured in the clinical setting, standardized procedures are required for sample collection to be of value.

Keywords: CPT2D; Free fatty acids; LCHADD; Long-chain fatty acid oxidation disorders; Plasma acylcarnitines; TFPD; VLCADD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism
  • Acetyl-CoA C-Acyltransferase / genetics
  • Acetyl-CoA C-Acyltransferase / metabolism
  • Acyl-CoA Dehydrogenase, Long-Chain / blood
  • Carbon-Carbon Double Bond Isomerases / genetics
  • Carbon-Carbon Double Bond Isomerases / metabolism
  • Cardiomyopathies / blood*
  • Cardiomyopathies / diet therapy
  • Cardiomyopathies / pathology
  • Cardiomyopathies / therapy
  • Carnitine / analogs & derivatives*
  • Carnitine / blood
  • Carnitine / genetics
  • Carnitine / metabolism
  • Carnitine O-Palmitoyltransferase / blood
  • Carnitine O-Palmitoyltransferase / deficiency*
  • Congenital Bone Marrow Failure Syndromes / blood*
  • Congenital Bone Marrow Failure Syndromes / diet therapy
  • Congenital Bone Marrow Failure Syndromes / pathology
  • Congenital Bone Marrow Failure Syndromes / therapy
  • Enoyl-CoA Hydratase / genetics
  • Enoyl-CoA Hydratase / metabolism
  • Exercise Therapy
  • Fasting
  • Female
  • Humans
  • Lipid Metabolism, Inborn Errors / blood*
  • Lipid Metabolism, Inborn Errors / diet therapy
  • Lipid Metabolism, Inborn Errors / pathology
  • Lipid Metabolism, Inborn Errors / therapy
  • Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase / blood
  • Male
  • Metabolism, Inborn Errors / blood*
  • Metabolism, Inborn Errors / diet therapy
  • Metabolism, Inborn Errors / pathology
  • Metabolism, Inborn Errors / therapy
  • Mitochondrial Diseases / blood*
  • Mitochondrial Diseases / diet therapy
  • Mitochondrial Diseases / pathology
  • Mitochondrial Diseases / therapy
  • Mitochondrial Myopathies / blood*
  • Mitochondrial Myopathies / diet therapy
  • Mitochondrial Myopathies / pathology
  • Mitochondrial Myopathies / therapy
  • Mitochondrial Trifunctional Protein / blood
  • Mitochondrial Trifunctional Protein / deficiency*
  • Muscular Diseases / blood*
  • Muscular Diseases / diet therapy
  • Muscular Diseases / pathology
  • Muscular Diseases / therapy
  • Nervous System Diseases / blood*
  • Nervous System Diseases / diet therapy
  • Nervous System Diseases / pathology
  • Nervous System Diseases / therapy
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism
  • Rhabdomyolysis / blood*
  • Rhabdomyolysis / diet therapy
  • Rhabdomyolysis / pathology
  • Rhabdomyolysis / therapy

Substances

  • acylcarnitine
  • fatty acid oxidation complex
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Long-Chain-3-Hydroxyacyl-CoA Dehydrogenase
  • Acyl-CoA Dehydrogenase, Long-Chain
  • Acetyl-CoA C-Acyltransferase
  • Mitochondrial Trifunctional Protein
  • Carnitine O-Palmitoyltransferase
  • Enoyl-CoA Hydratase
  • Racemases and Epimerases
  • Carbon-Carbon Double Bond Isomerases
  • Carnitine

Supplementary concepts

  • Carnitine palmitoyl transferase 2 deficiency
  • Trifunctional Protein Deficiency With Myopathy And Neuropathy
  • VLCAD deficiency