Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

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.

A Piece of the Puzzle—Possible Mechanisms for Why Low Dietary EPA and DHA Cause Hepatic Lipid Accumulation in Atlantic Salmon (Salmo salar)

“…However, a significantly higher accumulation of 3-hydroxyacylcarnitines was evident in fish fed diets 1.0 and 1.6 compared to diet 3.5 in the current study, which indicates dysfunction with 3-hydroxy-acyl-CoA-dehydrogenase (third step in mitochondrial β-oxidation) [50]. A disturbance of the mitochondrial membrane, suggested to have occurred in fish fed low EPA + DHA in the present study, could cause problems for this enzyme, as it is located on the mitochondrial membrane [51]. A general accumulation of acylcarnitines would be expected concomitant with hydroxylated acylcarnitines; however, the accumulation was less pronounced in fish fed diet 1.0 than diet 1.6.…”

Sex differences in the human metabolome

“…This could be partially legitimated by higher food intake in men. In addition, since AC variations are markers of metabolic and mitochondrial impairment in inborn errors of metabolism (including fatty acid β-oxidation disorders and organic acidemias, among others) [ 70 , 91 ], and are associated with increased risk of obesity, type-2 diabetes, and cardiovascular diseases [ 90 , 92 , 93 ], individuals in a good healthy state may not show a significant sexual dimorphism in AC patterns.…”

Highly conserved shifts in ubiquitin-proteasome system (UPS) activity drive mitochondrial remodeling during quiescence

“…These data are consistent with the reduced complex I activity previously observed in VDAC mutants 20 and suggest that mitochondrial membrane potential can be uncoupled from respiration during MRQ. Furthermore, our metabolomic analysis of VDAC-RNAi oocytes revealed a slightly altered metabolic signature, including some modest effects on FAO-related metabolites (3-hydroxysebacic acid, tetradecanoylcarnitine 21 ) in VDAC-RNAi oocytes (Supplementary Fig. 6D-F).…”