Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase.
Long chain acyl-CoA dehydrogenase (LCAD) has recently been shown to be the mitochondrial enzyme responsible for the beta-oxidation of branched chain and unsaturated fatty acids [Biochim. Biophys. Acta 1393 (1998) 35; Biochim. Biophys. Acta 1485 (2000) 121]. Whilst disorders of short, medium and very long chain acyl dehydrogenases are known, there is no known disorder of LCAD deficiency in humans. Experimental LCAD deficiency in mice shows an acyl-carnitine profile with prominent elevations of unsaturated fatty acid metabolites C14:1 and C14:2 [Hum. Mol. Genet. 10 (2001) 2069]. A child with autism whose acyl-carnitine profile also shows these abnormalities is presented, and it is hypothesized that the child may have LCAD deficiency. Additional metabolic abnormalities seen in this patient include alterations of TCA energy production, ammonia detoxification, reduced synthesis of omega-3 DHA, and abnormal cholesterol metabolism. These metabolic changes are also seen as secondary abnormalities in dysfunction of fatty acid beta-oxidation, and have also been reported in autism. It is hypothesized that LCAD deficiency may be a cause of autism. Similarities between metabolic disturbances in autism, and those of disorders of fatty acid beta-oxidation are discussed.
Clark-Taylor
Tonya
T
tbct@bigpond.net.au
Clark-Taylor
Benjamin E
BE
D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D001321:Autistic Disorder / Q000150:complications / Q000209:etiology* / Q000378:metabolism; D002648:Child; D004485:Eczema / Q000150:complications; D005227:Fatty Acids / Q000378:metabolism*; D005512:Food Hypersensitivity / Q000150:complications; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008962:Models, Theoretical; D010100:Oxygen / Q000378:metabolism*
D005227:Fatty Acids; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D010100:Oxygen