Fatty Acid Beta-Oxidation Disorders: A Brief Review

Abstract

Background: Mitochondrial fatty acid β-oxidation disorders (FAODs) are a heterogeneous group of defects in fatty acid transport and mitochondrial β-oxidation. They are inherited as autosomal recessive disorders and have a wide range of clinical presentations. Summary: The background information and case report provide important insight into mitochondrial FAODs. The article provides a wealth of information describing the scope of these disorders. Key Messages: This article presents a typical case of medium chain acyl-CoA dehydrogenase deficiency and summarizes the pathophysiology, clinical presentation, diagnosis and treatment of mitochondrial FAODs.

Proteomic signatures of in vivo muscle oxidative capacity in healthy adults

“…The current study shows that the TCA and β‐oxidation cycles are also significantly associated with better in vivo oxidative capacity. Importantly, our findings suggest that fatty acid oxidation disorder (Vishwanath, ) is one of the mechanisms involved in the decline of in vivo muscle oxidative capacity. Consistent with this notion, Bian and colleagues proposed that ACAD10 variation in Pima Indians may increase susceptibility to type 2 diabetes and that this effect may be mediated by impairment of insulin sensitivity via abnormal lipid oxidation (Bian et al, ).…”

The decreased level of plasma carnitine in patients with epilepsy

“…Эти патологические состояния достаточно часто сопровождаются эпилептическими приступами, и эпилепсия может быть даже первым симптомом заболеваний. При их лечении обязательным является назначение карнитина [10].…”

Medium-chain acyl-CoA dehydrogenase, a gatekeeper of mitochondrial function in glioblastoma multiforme

“…MCAD deficiency is a human inherited autosomal recessive disorder caused by inactivation of the ACADM gene. The presence of ACADM mutations is screened perinatally, and affected individuals who follow appropriate dietary recommendations can lead normal lives (Schatz and Ensenauer, 2010;Vishwanath, 2016). The most frequent mutation, K304E (~90%), as well as nearly all mutations identified in patients, whether in the catalytic or other domains, disrupt protein folding and prevent active tetrameric MCAD from stabilizing in the mitochondrial matrix (Schatz and Ensenauer, 2010;Vishwanath, 2016).…”

“…The presence of ACADM mutations is screened perinatally, and affected individuals who follow appropriate dietary recommendations can lead normal lives (Schatz and Ensenauer, 2010;Vishwanath, 2016). The most frequent mutation, K304E (~90%), as well as nearly all mutations identified in patients, whether in the catalytic or other domains, disrupt protein folding and prevent active tetrameric MCAD from stabilizing in the mitochondrial matrix (Schatz and Ensenauer, 2010;Vishwanath, 2016). Further, the role of ACADM in the pathogenesis of MCAD deficiency has been confirmed by the generation of an Acadm-deficient mouse model that shows similar clinical manifestations and histopathological characteristics (Tolwani et al, 2005).…”

“…Thus, in GBM, the activity of MCAD does not solely support cellular energetics as part of the β-oxidation cycle, but our work demonstrates a previously unappreciated protective role for MCAD fatty acid catabolism to clear toxic accumulations of lipid molecules that may otherwise cause lethal damage to the cell. Given that inherited MCAD deficiency is a condition compatible with normal quality of life, with individuals carrying genetic biallelic inactivation of its encoding gene (ACADM) requiring only dietary adjustment to thrive (Schatz and Ensenauer, 2010;Vishwanath, 2016), an actionable therapeutic opportunity exists to target MCAD in GBM patients.…”