title: Combined enzyme defect of mitochondrial fatty acid oxidation.
abstract: A young girl presented with recurrent episodes of muscle weakness culminating in a severe attack of generalized muscle weakness. In the muscle mitochondria from the patient there was an abnormal pattern of intermediates of beta-oxidation with an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters, and 3-oxoacylcarnitines. There was low activity of long-chain 3-hydroxyacyl-CoA dehydrogenase in mitochondria from all tissues. The activity of long-chain 2-enoyl-CoA hydratase was low in muscle mitochondria and 3-oxoacyl-CoA thiolase activity measured with 3-oxohexadecanoyl-CoA as substrate was low in fibroblast, muscle, and cardiac mitochondria but only partial deficiency was present when the activity was measured with 3-oxooctanoyl-CoA. The activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase in fibroblasts from the patient's parents was intermediate between those of controls and the patient. The patient has a combined defect of the long-chain 3-hydroxyacyl-CoA dehydrogenase, long-chain 3-oxoacyl-CoA thiolase, and long-chain 2-enoyl-CoA hydratase which appears to be inherited in an autosomal recessive manner. This suggests there is a multifunctional enzyme catalyzing these activities in human mitochondria and that this enzyme is deficient in our patient.
authors.affiliation: Division of Clinical Neuroscience, Medical School, University of Newcastle upon Tyne, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Jackson
authors.forename: R S
authors.initials: RS
authors.lastname: Kler
authors.forename: K
authors.initials: K
authors.lastname: Bartlett
authors.forename: H
authors.initials: H
authors.lastname: Briggs
authors.forename: L A
authors.initials: LA
authors.lastname: Bindoff
authors.forename: M
authors.initials: M
authors.lastname: Pourfarzam
authors.forename: D
authors.initials: D
authors.lastname: Gardner-Medwin
authors.forename: D M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D000328:Adult; D002675:Child, Preschool; D004746:Enoyl-CoA Hydratase / Q000172:deficiency*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009135:Muscular Diseases / Q000209:etiology; D010084:Oxidation-Reduction
chemical_list: D005227:Fatty Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase