32 - Inborn Errors of Mitochondrial Fatty Acid Oxidation

Summary

Mitochondrial fatty acid β-oxidation plays a major role in energy production and homeostasis once glycogen stores are depleted because of fasting, illness, and increased muscular activity [1]. The mitochondrial β-oxidation of fatty acids provides nearly 80% of energy for cardiac and hepatic functions at all times [2]. In the liver, the β-oxidation of fatty acids generates the precursors of ketone bodies, 3-hydroxybutyrate, and acetoacetate which are used as alternate fuel by the brain and peripheral tissues, such as cardiac and skeletal muscle, when glucose supply is low [3].

Defects in the mitochondrial fatty acid oxidation pathway are inherited as autosomal recessive disorders. The first well-documented genetic defect of fatty acid oxidation (FAO), described in 1973, was carnitine palmitoyl transferase (CPT) deficiency, presenting as a skeletal muscle disorder with exercise-induced rhabdomyolysis and myoglubinuria [4]. More than 20 defects have since been discovered [2]. The growing number of FAO disorders covers a wide spectrum of phenotypes, and the disorders are characterized by a wide array of clinical presentations. FAO disorders have become an important group of inherited metabolic disorders causing morbidity and mortality. FAO disorders, if unrecognized and untreated, may cause sudden unexpected death. Previously described clinical entities such as Reye's syndrome, certain cases of sudden infant death syndrome (SIDS), cyclic vomiting syndrome, unexplained cases of liver failure, and maternal complications of pregnancy are examples of disorders associated with defects in FAO [2].