A short introduction to acyl-CoA dehydrogenases; deficiencies and novel treatment strategies

Abstract

Introduction: The acyl-CoA dehydrogenases (ACADs) have a central role in the catabolism of fatty acids and amino acids, and the production of chemical energy in the form of ATP. Genetic defects which cause a deficiency of functional ACAD enzymes result in a series of disorders with a spectrum of phenotypes, with severity ranging from asymptomatic to multiple organ failure and sudden death. The ACAD flavoprotein family catalyzes the initial step of the oxidation of certain fatty acid and amino acid CoA conjugates. The enzymatic reaction consists of an oxidative and a reductive sub-reaction, which ultimately transfers an electron to flavin adenine dinucleotide (FAD), which can then pass on the electron to the respiratory chain for ATP production.Areas covered: Newborn screening for some of the more common ACAD deficiencies has been introduced in several countries; the diagnosis of asymptomatic patients will be briefly discussed. To improve treatment of some ACADs, several novel ACAD treatment strategies have been proposed. These target different regulator points of ACAD function.Expert opinion: A better understanding of the pathophysiological pathways involved in each ACAD disorder will be required for better treatment; different strategies to achieve this are discussed.