Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A female infant was seen at the age of 2 months because of hypotonia, delayed motor development, and lactic acidosis, and she died at age 13 months due to respiratory failure. In a muscle specimen taken at 11 months and in a liver specimen obtained 1.5 hours postmortem, we found decreased activities of cytochrome c oxidase and long-chain acyl coenzyme A dehydrogenase. Neuropathological changes were typical for Leigh's subacute necrotizing encephalomyelopathy. To our knowledge, this is the first report of a combined defect of complex IV of the respiratory chain and of the long-chain specific acyl coenzyme A dehydrogenase of beta-oxidation in muscle and liver.
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PMID:Cytochrome c oxidase deficiency and long-chain acyl coenzyme A dehydrogenase deficiency with Leigh's subacute necrotizing encephalomyelopathy. 131 9

Two siblings are reported who were symptomatic in the neonatal period. The first died suddenly at 4 days of age after regurgitating a meal. The postmortem examination showed steatosis of the liver, kidney and muscle. In the second, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was diagnosed at 3 days of age with muscular hypotonia, vomiting, hyperammonaemia and mild acidosis. Thus disorders of fatty acid oxidation should also be considered in newborns. The biochemical work up indicates that in neonates, analysis of serum medium-chain fatty acids and of acyl and free carnitine are more likely to lead to a diagnosis than determining dicarboxylic acids alone in urine. Long-term treatment was effective and monitored by the acyl/free carnitine ratio.
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PMID:Early diagnosis and treatment of neonatal medium-chain acyl-CoA dehydrogenase deficiency: report of two siblings. 234 56

The clinical and pathologic findings in 12 patients with medium-chain acyl CoA dehydrogenase deficiency and three patients with long-chain acyl CoA dehydrogenase deficiency are summarized. Although these inborn errors of intramitochondrial beta-oxidation of fatty acids present with similar findings to Reye's syndrome, there are clinical, laboratory and hepatic histologic differences. Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency. Long-chain acyl CoA dehydrogenase deficiency is differentiated from medium-chain acyl CoA dehydrogenase deficiency by younger age at presentation, more profound cardiorespiratory depression, evidence of cardiomyopathy, and sequelae of muscle weakness, hypotonia and developmental delay. Definitive diagnosis is made by assay of medium-chain or long-chain enzyme activity in cultured skin fibroblasts or in leukocytes. Hepatic light microscopic alterations are essentially limited to steatosis, which may be either macro- or microvesicular. The cases with microvesicular steatosis can be differentiated morphologically from Reye's syndrome by electron microscopy, showing the absence of the mitochondrial changes characteristic of Reye's. Four of seven cases of acyl CoA dehydrogenase deficiency showed some variations from normal in the appearance of the hepatocyte mitochondria. The relationship of these variations to the basic metabolic defect(s) remains to be determined.
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PMID:Medium-chain and long-chain acyl CoA dehydrogenase deficiency: clinical, pathologic and ultrastructural differentiation from Reye's syndrome. 379 3

Three children from unrelated families presented in early childhood with hypoglycemia and cardiorespiratory arrests associated with fasting. Significant hepatomegaly, cardiomegaly, and hypotonia were present at the time of initial presentation. Ketones were not present in the urine at the time of hypoglycemia in any patient; however, dicarboxylic aciduria was documented in one patient at the time of the acute episode and in two patients during fasting studies. Total plasma carnitine concentration was low with an increased esterified carnitine fraction. These findings suggested a defect in mitochondrial fatty acid oxidation, and specific assays were performed for the acyl coenzyme A (CoA) dehydrogenases. These analyses showed that the activity of the long-chain acyl CoA dehydrogenase was less than 10% of control values in fibroblasts, leukocytes, and liver tissue. Activities of the medium-chain, short-chain, and isovaleryl CoA dehydrogenases were not different from control values. With cultured fibroblasts, CO2 evolution from long-chain fatty acids was significantly reduced, while CO2 evolution from medium-chain and short-chain fatty acids was comparable to control values--findings consistent with a defect early in the beta-oxidation sequence. Studies of acyl CoA dehydrogenase activities in fibroblasts and leukocytes from parents of the patients showed levels of long-chain acyl CoA dehydrogenase activity intermediate between affected and control values and indicated an autosomal recessive form of inheritance of this enzymatic defect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia. 402 72

The in vivo oxidation of fatty acids (FA) of different chain length was investigated in three patients with documented mitochondrial FA oxidation disorders: one patient with mild multiple acyl-CoA dehydrogenase deficiency (MADM), one with medium chain acyl-CoA dehydrogenase deficiency (MCAD), and one with carnitine palmitoyltransferase I deficiency (CPT I). Breath tests were performed after oral administration of 1-13C butyric. 1-13C octanoic, and 1-13C palmitic acids. 13C/12C ratio in the expired oxidative end product CO2 was measured. The cumulative 13C elimination was calculated and expressed as a percentage of the administered dose. In the MADM patient the influence of carnitine therapy (or deprivation) on the utilization of 1-13C palmitic acid was also examined. In the MCAD and CPT I patients, the 1-13C butyric, 1-13C octanoic and 1-13C palmitic acids in vivo oxidation were similar to five healthy controls. In the MADM patient, the oxidation of 1-13C butyric and 1-13C octanoic acids were normal, whereas the metabolism of 1-13C palmitic acid ranged from 33% of 66% of controls. In this patient the serum carnitine level decreased from 60 to 27 mumol/l without carnitine supplementation. Clinically there was mild hypotonia. 1-13C palmitic acid oxidation compared to controls was 50%. After 2 further weeks of carnitine deprivation the serum carnitine was 10-15 mumol/l. Clinically he was very hypotonic and had a large liver. 1-13C Palmitic acid oxidation was 33%. After 6 weeks of readministration of carnitine (L-carnitine 100 mg/kg/day p.o.) the serum carnitine was 60 mumol/l and the patient was in good clinical condition. 1-13C palmitic acid oxidation was 66% compared to controls. Our study implies that this simple fatty acid breath test is not of diagnostic use for detection of enzymatic defects in FA oxidation disorders. The carnitine dependent 1-13C palmitic acid oxidation indicates that this test might be of some value in cases with primary or secondary carnitine deficiencies.
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PMID:In vivo stable isotope studies in three patients affected with mitochondrial fatty acid oxidation disorders: limited diagnostic use of 1-13C fatty acid breath test using bolus technique. 926 22

A 9-month-old boy with presented generalised hypotonia, severe cardiomyopathy, and massive liver enlargement following 10 days of viral gastroenteritis. He was diagnosed with very long-chain acyl-CoA dehydrogenase deficiency and has been successfully treated.
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PMID:Very long-chain acyl-CoA dehydrogenase deficiency in an infant presenting with massive hepatomegaly. 1222 61

Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48 hours postpartum, with a previous history of early death (day 2) in siblings with a history of parental consanguinity; somnolence, inactivity, refusal to suck within 24 h, hepatomegaly, persistent hypoglycemia, hypocalcemia, hyperkalemia and severe metabolic acidosis prior to cardiac arrest. Dried blood spots by tandem mass spectrometry demonstrated 10 x elevation of palmitoylcarnitine, moderate elevation of oleylcarnitine, steroylcarnitine and myristoylcarnitine. Case 2. Medium chain acyl CoA dehydrogenase (MCAD) deficiency. (OMIM 212139) A six-week-old male infant, developed sudden cardiac arrest after contacting a viral illness, resuscitated successfully in the first episode, only to succumb during the second episode, 2 weeks apart. Plasma acylcarnitine via tandem mass spectrometry was reported normal; however, urine organic acids via gas liquid chromatography and mass spectrometry demonstrated characteristic metabolites consistent with MCADD. Case 3. Carnitine deficiency, systemic primary. (CDSP) (OMIM 212140) A one-year-old girl with progressive dyspnea since birth and a history of parental consanguinity. Severe dilated cardiomyopathy with episodes of cardiac decompensations, hepatomegaly, anemia, generalized hypotonia, but no hypoglycemia were demonstrated prior to cardiac arrest. Extremely low carnitine level noted in dried blood spots via tandem mass spectrometry.
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PMID:Mitochondrial fatty acid oxidation disorders in Thai infants: a report of 3 cases. 1240 51

A two-year-three-month old girl was hospitalized for detailed examination following repeated hyper-creatine kinasemia and cervical muscle cramps induced by pyrexia and persistent hypertonicity of the cervical muscles. Physical examination showed mild hypotonia but no muscle weakness. Induction of symptoms by continuous cervical muscular exercise and the appearance of dicarboxylic aciduria during the fasting test indicated a disorder of fatty acid oxidation. Free fatty acid and acyl carnitine analyses using dried blood spots, and acyl-CoA dehydrogenase activity assays using cultured skin fibroblasts established a diagnosis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Currently VLCAD deficiency has been divided into three phenotypes; a severe childhood form, a milder childhood form, and an adult form. However, we suggest that the severe and milder childhood forms would be better described as a systemic form, and the adult form and our infant case as a myopathic form. An early onset of the myopathic form within the first year of life, as well as its diagnosis in early infancy, has never been described in the literature.
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PMID:[A two-year-old infant with a myopathic form of very-long-chain Acyl-CoA dehydrogenase deficiency]. 1463 45

Defects of mitochondrial beta-oxidation are a growing group of disorders with variable clinical presentations ranging from mild hypotonia to sudden infant death. Current therapy involves avoidance of fasting, dietary restrictions, and cofactor supplementation. Unfortunately, times of acute illness and noncompliance can interfere with these therapies and result in a rapid clinical decline. The development of a safe, durable, and effective gene delivery system remains an attractive alternative therapy for individuals with these disorders. To this end, a recombinant first-generation adenovirus vector (Ad/cmv-hMCAD) has been prepared that constitutively expresses the human medium chain acyl CoA dehydrogenase (MCAD) protein under the control of the CMV promoter and bovine polyadenylation signal. Characterization of human fibroblasts deficient in MCAD infected with Ad/cmv-hMCAD including Western analysis, immunohistological staining visualized with confocal microscopy, electron transfer protein (ETF) reduction assay, and palmitate loading studies was performed. Infection of MCAD deficient fibroblast with Ad/cmv-hmcad resulted in the production of a 55kDa protein that co-localized in cells with a mitochondrial marker. Extracts prepared from Ad/cmv-hMCAD infected deficient fibroblasts demonstrated correction of the block seen in the MCAD catalyzed reduction of ETF in the presence of octanoyl CoA. Finally, MCAD deficient fibroblasts infected with increasing amounts of Ad/cmv-hMCAD showed a stepwise improvement of the abnormal acylcarnitine profile exhibited by the deficient cells. Together these studies demonstrate our ability to express and monitor the expression of MCAD in treated cells and support further in vivo murine studies to assess toxicity and duration of correction with this and other MCAD recombinant vectors.
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PMID:In vitro correction of medium chain acyl CoA dehydrogenase deficiency with a recombinant adenoviral vector. 1589 52

Short-chain acyl-CoA dehydrogenase (SCAD) is a mitochondrial enzyme that catalyzes the dehydrogenation of short chain fatty acids (4 to 6 carbons in length) thereby initiating the cycle of beta-oxidation. This process generates acetyl-CoA, the key substrate for hepatic ketogenesis or ATP production by the Kreb's cycle. A deficiency of SCAD results in the build-up of potentially cytotoxic metabolites including ethylmalonic acid, methylsuccinyl CoA and butyryl-carnitine. The end-organ involvement is heterogeneous, but most commonly includes hypotonia with possible lipid myopathy and developmental delay. Other reported complications include dysmorphic craniofacial features, hypoglycemia, seizures, scoliosis, hypertonia and hyperreflexia, cyclic vomiting and myocardial dysfunction. We present a 23-month-old girl with SCAD deficiency, who required posterior fossa decompression for type 1 Chiari malformation. The potential perioperative implications of SCAD deficiency are reviewed.
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PMID:Perioperative management of a child with short-chain acyl-CoA dehydrogenase deficiency. 1610 9


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