Short-chain acyl-coenzyme A dehydrogenase deficiency. Clinical and biochemical studies in two patients.
We describe two patients with short-chain acyl-coenzyme A (CoA) dehydrogenase (SCADH) deficiency. Neonate I excreted large amounts of ethylmalonate and methylsuccinate; ethylmalonate excretion increased after a medium-chain triglyceride load. Neonate II died postnatally and excreted ethylmalonate, butyrate, 3-hydroxybutyrate, adipate, and lactate. Both neonates' fibroblasts catabolized [1-14C]butyrate poorly (29-64% of control). Neonate I had moderately decreased [1-14C]octanoate catabolism (43-60% of control), while neonate II oxidized this substrate normally; both catabolized radiolabeled palmitate, succinate, and/or leucine normally. Cell sonicates from neonates I and II dehydrogenated [2,3-3H]butyryl-CoA poorly (41 and 53% of control) and [2,3-3H]octanoyl-CoA more effectively (59 and 95% of control). Mitochondrial acyl-CoA dehydrogenase (ADH) activities with butyryl- and octanoyl-CoAs were 37 and 56% of control in neonate I, and 47 and 81% of control in neonate II, respectively. Monospecific medium-chain ADH (MCADH) antisera inhibited MCADH activity towards both butyryl- and octanoyl-CoAs, revealing SCADH activities to be 1 and 11% of control for neonates I and II, respectively. Fibroblast SCADH and MCADH activities were normal in an adult female with muscular SCADH deficiency.
D020155:3-Hydroxybutyric Acid; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency*; D000272:Adipates / Q000652:urine; D000328:Adult; D002087:Butyrates / Q000652:urine; D020148:Butyric Acid; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006885:Hydroxybutyrates / Q000652:urine; D007773:Lactates / Q000652:urine; D019344:Lactic Acid; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology* / Q000652:urine; D008314:Malonates / Q000652:urine; D013386:Succinates / Q000652:urine
D000272:Adipates; D002087:Butyrates; D006885:Hydroxybutyrates; D007773:Lactates; D008314:Malonates; D013386:Succinates; D020148:Butyric Acid; D019344:Lactic Acid; C038080:ethylmalonic acid; C029900:adipic acid; D044944:Acyl-CoA Dehydrogenases; C039138:methylsuccinic acid; D020155:3-Hydroxybutyric Acid