Abstract
Mitochondrial fatty acid β-oxidation (FAO) contributes a large proportion to the body’s energy needs in fasting and in situations of metabolic stress. Most tissues use energy from fatty acids, particularly the heart, skeletal muscle and the liver. In the brain, ketone bodies formed from FAO in the liver are used as the main source of energy. The mitochondrial fatty acid oxidation disorders (FAODs), which include the carnitine system defects, constitute a group of diseases with several types and subtypes and with variable clinical spectrum and prognosis, from paucisymptomatic cases to more severe affectations, with a 5% rate of sudden death in childhood, and with fasting hypoketotic hypoglycemia frequently occurring. The implementation of newborn screening programs has resulted in new challenges in diagnosis, with the detection of new phenotypes as well as carriers and false positive cases. In this article, a review of the biochemical markers used for the diagnosis of FAODs is presented. The analysis of acylcarnitines by MS/MS contributes to improving the biochemical diagnosis, both in affected patients and in newborn screening, but acylglycines, organic acids, and other metabolites are also reported. Moreover, this review recommends caution, and outlines the differences in the interpretation of the biomarkers depending on age, clinical situation and types of samples or techniques.
Highlights
The correct diagnosis of patients has been difficult for many years, since there has been a lack of adequate biomarkers in the blood, serum or plasma, and of enzymatic assays that allow the specification of a definite fatty acid oxidation disorders (FAODs) [17]
Very long-chain acyl-CoA dehydrogenase (VLCAD) is one of the four acyl-CoA dehydrogenases with different chain length specificities, and it catalyzes the first stage of fatty acid β-oxidation (FAO)
The knowledge about and study of biomarkers of FAODs in patients suspected of harboring them is a powerful tool for the characterization of these disorders
Summary
Fatty acid β-oxidation (FAO) of 20 carbons or less in length occurs in the mitochondria. In children after 12–24 h of fasting and in situations of metabolic stress, in which it is necessary to supply the energy of glucose once the glycogen stores have been depleted, FAO provides 80% of the body’s energy needs, mobilizing fatty acids (FAs) from adipose tissue. More than 25 enzymes and transporters are involved in the FAO pathway and the final product is acetyl-CoA, which can be used in the synthesis of ketone bodies or in the mitochondrial electron transport chain through the Krebs cycle to form ATP. In order to be able to pass to the mitochondrial matrix after cell uptake, long-chain fatty acids (LCFA, C14-C20) need to be activated into acyl-CoA esters by acyl-CoA synthetase (AS), which is found in the internal phase of the outer mitochondrial membrane.
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