Disorders of mitochondrial fatty acyl-CoA beta-oxidation

In recent years tremendous progress has been made with respect to the enzym ology of the mitochondrial fatty acid beta-oxidation machinery and defects therein. Firstly, a number of new mitochondrial beta-oxidation enzymes have been identified, including very-long-chain acyl-CoA dehydrogenase (VLCAD) and mitochondrial trifunctional protein (MTP). Secondly, the introduction o f tandem MS for the analysis of plasma acylcarnitines has greatly facilitat ed the identification of patients with a defect in fatty acid oxidation (FA O). These two developments explain why the number of defined FAO disorders has increased dramatically, making FAO disorders the most rapidly growing g roup of inborn errors of metabolism. In this review we describe the current state of knowledge of the enzymes involved in the mitochondrial oxidation of straight-chain, branched-chain and (poly)unsaturated fatty acyl-CoAs as well as disorders of fatty acid oxidation. The laboratory diagnosis of thes e disorders is described, with particular emphasis on the methods used to i dentify the underlying enzyme defect and the molecular mutations. In additi on, a simple flowchart is presented as a guide to the identification of mit ochondrial FAO-disorders. Finally, treatment strategies are discussed brief ly.