Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases

Mitochondrial fatty acid beta-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.

Automated summary

Mitochondrial fatty acid beta-oxidation disorders, including various types and subtypes, present a diverse clinical spectrum and prognosis. The implementation of newborn screening programs has brought new challenges to diagnosis and improved the accuracy of biochemical diagnosis. Interpretation of biomarkers requires caution, considering age, clinical situation, and types of samples or techniques.