acyl-CoA dehydrogenation deficiencies
Acyl-CoA dehydrogenation deficiencies are defined as disorders of the metabolism of branched chain and straight chain acyl-CoA esters and of glutaryl-CoA. The acyl-CoA dehydrogenation process is comprised of three enzymes, i.e. acyl-CoA dehydrogenase (isovaleryl-CoA, isobutyryl-CoA/2-Me-butyryl-CoA, short-chain acyl-CoA, general (medium-chain) acyl-CoA, long-chain acyl-CoA or glutaryl-CoA), electron transfer flavoprotein (ETF) and electron transfer flavoprotein dehydrogenase (ETF DH). Patients with isovaleryl-CoA dehydrogenase deficiency, glutaryl-CoA dehydrogenase deficiency and general (medium-chain) acyl-CoA dehydrogenase deficiency have been reported. Assays for the enzymatic diagnosis in cells from such patients (especially cultured skin fibroblasts) have been developed and the different methods are reviewed. Patients with apparent defects in all acyl-CoA dehydrogenation processes, designated multiple acyl-CoA dehydrogenation deficiencies, have also been found. I. e. glutaric aciduria type II, ethylmalonicadipic aciduria and riboflavin responsive multiple acyl-CoA dehydrogenation defect. The enzymatic diagnosis has not yet been performed in any of these cases, but the different approaches in this respect are discussed. The excretion pattern of organic acids in urine from patients with acyl-CoA dehydrogenation deficiencies - as measured by means of gas chromatography/mass spectrometry - offers in most cases a tentative diagnosis of the enzyme defect. These excretion patterns are characterized by the presence in urine of different compounds originating from the primary accumulated acyl-CoA ester(s).
The most important biochemical processes involved in the formation of these patterns seem to be glycine conjugation, omega-and omega-1-oxidation, carboxylation and dioxygenation.
The enzymatic basis for these processes is discussed with respect to the enzyme affinities for acyl-CoA esters relevant to the acyl-CoA dehydrogenation deficiencies.
Differential diagnosis
Reye syndrome