Fatty acyl-CoA dehydrogenase deficiency: enzyme measurement and studies on alternative metabolism

Fatty acyl-CoA dehydrogenase deficiencies are defined as disorders of the metabolism of straight chain acyl-CoA esters at the level of short chain acyl-CoA, general (medium chain) acyl-CoA and long chain acyl-CoA dehydrogenases. Patients with proven or indicated defects in either general (medium chain) or long chain acyl-CoA dehydrogenase have been reported. In recent years assays for the enzymatic diagnosis in cells, especially cultured skin fibroblasts, from such patients have been developed. The different methods are reviewed. The urinary excretion profile of organic acids from patients with fatty acyl-CoA dehydrogenase deficiencies are characterized by the presence of different compounds originating from the primary accumulated acyl-CoA ester(s). The most important biochemical processes involved in the formation of these compounds are glycine conjugation and omega/omega-1 oxidation. The biochemistry of these pathways is discussed and the knowledge gained from in vitro and in vivo studies is used to explain the excretion pattern in some of the patients with general (medium chain) acyl-CoA dehydrogenase deficiency.