Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.1.8 (acyl-CoA dehydrogenase)
 785 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiomyopathy and leukodystrophy are life-threatening complications of multiple acyl-CoA dehydrogenase deficiency (MADD). A 2-year-old boy with this disorder developed rapidly progressive leukodystrophy resulting in complete paralysis within 4 months. Within a week of starting sodium-D,L-3-hydroxybutyrate he had improved. After 2 years, neurological function returned, including walking independently, with progressive improvement of brain MRI. Two additional infants with MADD developed life-threatening cardiomyopathy unresponsive to conventional treatment. On sodium-D,L-3-hydroxybutyrate treatment their cardiac contractility showed progressive and sustained improvement. D,L-3-hydroxybutyrate is a therapeutic option for cerebral and cardiac complications in severe fatty acid oxidation defects.
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PMID:D,L-3-hydroxybutyrate treatment of multiple acyl-CoA dehydrogenase deficiency (MADD). 1272 99

Ethylmalonic encephalopathy (EE) is a rare, recently defined inborn error of metabolism which affects the brain, gastrointestinal system and peripheral blood vessels and is characterized by a unique constellation of clinical and biochemical features. A 7-month-old male, who presented with psychomotor retardation, chronic diarrhea and relapsing petechiae is described with the objective of highlighting the biochemical and neuroradiological features of this disorder as well as the effect of high-dose riboflavin therapy. Urinary organic acid analysis revealed markedly increased excretion of ethylmalonic acid, isobutyrylglycine, 2-methylbutyrylglycine and isovalerylglycine. Acylcarnitine analysis in dried blood spots showed increased butyrylcarnitine. Short-chain acyl-CoA dehydrogenase (SCAD) activity in muscle was normal as were mitochondrial OXPHOS enzyme activities in cultured skin fibroblasts. In skeletal muscle the catalytic activity of complex II was decreased. Brain MRI revealed bilateral and symmetrical atrophy in the fronto-temporal areas, massive enlargement of the subarachnoid spaces and hyperdensities on T (2) sequences of the basal ganglia. Mutation analysis of the ETHE1 gene demonstrated homozygosity for the Arg163Gly mutation, confirming the diagnosis of EE at a molecular level. On repeat MRI, a significant deterioration was seen, correlating well with the clinical deterioration of the patient.
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PMID:Ethylmalonic encephalopathy: clinical and biochemical observations. 1771 31

We report on a 6-year-old girl who presented at 6 months of age with seizures, delayed psychomotor development and mild facial dysmorphism. A small muscular ventricular septal defect was documented on echocardiogram and brain MRI showed a frontal brain anomaly. Urine organic acid analysis revealed dicarboxylic aciduria, and plasma acylcarnitine analysis showed marked elevation of octanoyl (C8) and decanoyl (C10) carnitines with C8:C10 ratio of 9:1. These results were indicative of medium chain acyl-CoA dehydrogenase deficiency. ACADM gene sequencing showed an apparent homozygous c.166G > C (Ala31Pro) missense mutation in exon 3; however, only the mother was found to be a carrier of this novel missense mutation. This finding along with non-regressive developmental delay prompted further karyotype and genomic investigations. An interstitial deletion of chromosome 1 was detected by repeat G-banding: 46,XX,del(1)(p22.2p31.1). Parental karyotypes were normal. The deletion was characterized by array CGH analysis using a 1 Mb BAC/PAC array platform. Clones deleted extended from RP11-88B10 (1p31.1) to RP5-1007M22 (1p22.2), a 15.5 Mb deletion which includes the ACADM locus. Clinical review of 6/7 cases of interstitial deletions with breakpoints of 1p22 and 1p31/32, including the patient in this report, indicate a variable phenotype. Thus, although G-band breakpoints are similar, common breakpoints for these alterations are unlikely. This is the first report of a patient with fatty acid oxidation defect caused by a mutation in combination with an interstitial chromosomal deletion.
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PMID:Interstitial deletion of 1p22.2p31.1 and medium-chain acyl-CoA dehydrogenase deficiency in a patient with global developmental delay. 1847 88

Elevated levels of cardiac mitochondrial uncoupling protein 3 (UCP3) and decreased cardiac efficiency (hydraulic power/oxygen consumption) with abnormal cardiac function occur in obese, diabetic mice. To determine whether cardiac mitochondrial uncoupling occurs in non-genetic obesity, we fed rats a high fat diet (55% kcal from fat) or standard laboratory chow (7% kcal from fat) for 3 weeks, after which we measured cardiac function in vivo using cine MRI, efficiency in isolated working hearts and respiration rates and ADP/O ratios in isolated interfibrillar mitochondria; also, measured were medium chain acyl-CoA dehydrogenase (MCAD) and citrate synthase activities plus uncoupling protein 3 (UCP3), mitochondrial thioesterase 1 (MTE-1), adenine nucleotide translocase (ANT) and ATP synthase protein levels. We found that in vivo cardiac function was the same for all rats, yet oxygen consumption was 19% higher in high fat-fed rat hearts, therefore, efficiency was 21% lower than in controls. We found that mitochondrial fatty acid oxidation rates were 25% higher, and MCAD activity was 23% higher, in hearts from rats fed the high fat diet when compared with controls. Mitochondria from high fat-fed rat hearts had lower ADP/O ratios than controls, indicating increased respiratory uncoupling, which was ameliorated by GDP, a UCP3 inhibitor. Mitochondrial UCP3 and MTE-1 levels were both increased by 20% in high fat-fed rat hearts when compared with controls, with no significant change in ATP synthase or ANT levels, or citrate synthase activity. We conclude that increased cardiac oxygen utilisation, and thereby decreased cardiac efficiency, occurs in non-genetic obesity, which is associated with increased mitochondrial uncoupling due to elevated UCP3 and MTE-1 levels.
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PMID:A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart. 2131 95