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 term neonate became lethargic and hypotonic at 46 hours of age and died 10 hours later despite supportive therapy. Urinary organic acids indicated medium-chain acyl-coenzyme A dehydrogenase deficiency, and DNA studies confirmed this disorder. Neonatal symptoms in this enzyme deficiency have rarely been reported, and recent reviews have ignored or discounted this presentation.
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PMID:A fatal neonatal case of medium-chain acyl-coenzyme A dehydrogenase deficiency with homozygous A-->G985 transition. 144 68

A case of severe hypoglycaemia precipitated by fasting in a child is described. As a result of the hypoglycaemia, the patient became brain damaged. The mechanism causing the hypoglycaemia was a defect in the fatty acid beta-oxidation enzyme, the connecting link acyl-CoA dehydrogenase. During a prolonged fast, fatty acids are not converted to acetyl-CoA and ketone bodies which participate in Kreb's cycle for production of energy to a sufficient extent. This result in non-ketotic hypoglycaemia with excretion of organic acids in the urine. As a rule, the symptoms occur for the first time during the first to second years of life in connection with common infectious diseases, with vomiting followed by clouding of consciousness and possibly coma, but the condition may also present with sudden unexpected death. Treatment consists of intravenous glucose. The diagnosis is established by testing the urine for hexanoylglycin and other substances and is confirmed by culture of skin fibroblasts and measurement of beta-oxidation activity. The disease is an autosomally recessive inherited condition. In families where there have been cases of unexplained hypoglycaemia and clouding of consciousness and cases of unexplained death in infancy or "near misses", all of the family members should be offered examination for the above mentioned enzyme deficiency.
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PMID:[Severe hypoglycemia and clouding of consciousness caused by deficiency of the connecting link acyl CoA dehydrogenase]. 200 Jun 54

Two patients with hypoketotic hypoglycaemia and dicarboxylic aciduria are described. Studies of their urinary organic acids by gas chromatography-mass spectrometry (GC-MS) showed an excretion of dicarboxylic acids (adipic suberic and sebacic acids), unsaturated dicarboxylic acids (cis-octenedioic and decenedioic acids),5-hydroxyhexanoic acid, hexanoyl-glycine and suberylglycine. Deficiency of the medium chain acyl-CoA dehydrogenase (MCAD) in fibroblasts was documented for both children. Despite a similar presentation (hypoglycaemic coma), organic acid profile (dicarboxylic aciduria and suberylglycine excretion) and enzyme deficiency (MCAD), they did not respond similarly to glucose infusion.
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PMID:Gas chromatography--mass spectrometry (GC--MS) diagnosis of two cases of medium chain acyl-CoA dehydrogenase deficiency. 643 44

We report a novel mild variant of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) diagnosed in four infants who, in neonatal screening, showed abnormal acylcarnitine profiles indicative of MCADD. Three patients showed completely normal urinary organic acids and phenylpropionic acid loading tests were normal in all four patients. Enzyme studies showed residual MCAD activities between "classical" MCADD and heterozygotes. ACADM gene analysis revealed compound heterozygosity for the common mutation K329E and a novel mutation, Y67H, in two cases, and homozygosity for mutation G267R and the novel mutation S245L, respectively, in two children of consanguineous parents. As in other metabolic disorders, the distinction between "normal" and "disease" in MCAD deficiency is blurring into a spectrum of enzyme deficiency states caused by different mutations in the ACADM gene potentially influenced by factors affecting intracellular protein processing.
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PMID:Molecular and functional characterisation of mild MCAD deficiency. 1140 68

Long-chain acyl-CoA dehydrogenase (LCAD) deficiency has not been found in human patients. There has been an LCAD deficient (LCAD-/-) mouse model developed via gene targeting strategies that has gestational loss as a part of its phenotype. We tested the hypothesis that LCAD deficiency disrupts normal embryonic development and explains at least in part the gestational loss in the mouse and may suggest a mechanism to explain the lack of any human patients with this inherited enzyme deficiency. We cultured and evaluated embryos with three different genotypes: LCAD+/+, LCAD+/-, and LCAD-/-. We found a significantly increased rate of death (P<0.012) in LCAD-/- embryos at the morula-to-blastocyst conversion indicating a deficient ability to complete the development of a blastocoele and formation of a blastocyst. Furthermore, we hypothesized that we could rescue LCAD-/- embryos in culture by supplying excess fatty acids of chain-lengths that could be readily oxidized by them despite their inherited enzyme deficiency. We were unable, however, to demonstrate any rescue by supplementing the culture medium with fatty acids of a wide-range of chain-lengths. Therefore, overall we demonstrated a severely deficient capacity for LCAD-/- embryos to develop past the morula stage with intermediate rates of development found in the LCAD+/- embryos as compared to the LCAD+/+ embryos. Furthermore, we were unable to rescue the LCAD-/- embryos with any fatty acid supplementation.
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PMID:Disrupted blastocoele formation reveals a critical developmental role for long-chain acyl-CoA dehydrogenase. 1530 24

Fasting-induced metabolic disease of all inherited deficiencies of the acyl-CoA dehydrogenases is characterized by hypoglycemia, hypoketonemia, and organic aciduria. Mice with these enzyme deficiencies are cold intolerant. To evaluate the potential role that dietary fatty acid chain-length has on a patient's ability to compensate during a metabolic challenge, we fed long-chain acyl CoA dehydrogenase (LCAD) deficient and short-chain acyl CoA dehydrogenase (SCAD) deficient mice a diet rich in medium-chain triglycerides (MCT) or long-chain triglycerides (LCT). To elucidate the importance of maintaining adequate serum glucose concentrations on compensation mechanisms during metabolic challenge, we treated LCAD-/- mice with a solution of 12.5% glucose or saline prior to fasting and a cold-challenge. We found that feeding SCAD deficient mice the LCT diet from weaning increased survival from 40 to 94% during metabolic challenge of cold tolerance. In contrast, there was no benefit to feeding the MCT diet at weaning to LCAD-/- mice; however, there was significant benefit when LCAD-/- mice were fed the MCT diet from the beginning of gestation. Survival during cold-challenge increased from 50 to 93%. In the LCAD-/- mice treated with glucose, despite maintaining serum glucose concentrations at normal or higher concentrations, the LCAD-/- mice were still unable to compensate during metabolic challenge. These results indicate the important influences dietary fatty acids may have by providing enhanced metabolic tolerance in patients with inborn errors of fatty acid oxidation. Furthermore, these studies demonstrate that there may be crucial variables involved in the treatment of these patients, including the patient's specific enzyme deficiency, the quantity and chain-length of dietary fat, which may provide positive effects, as well as the time in development when it was administered.
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PMID:Influence of dietary fatty acid chain-length on metabolic tolerance in mouse models of inherited defects in mitochondrial fatty acid beta-oxidation. 1558 19

Published data on treatment of fatty acid oxidation defects are scarce. Treatment recommendations have been developed on the basis of observations in 75 patients with long-chain fatty acid oxidation defects from 18 metabolic centres in Central Europe. Recommendations are based on expert practice and are suggested to be the basis for further multicentre prospective studies and the development of approved treatment guidelines. Considering that disease complications and prognosis differ between different disorders of long-chain fatty acid oxidation and also depend on the severity of the underlying enzyme deficiency, treatment recommendations have to be disease-specific and depend on individual disease severity. Disorders of the mitochondrial trifunctional protein are associated with the most severe clinical picture and require a strict fat-reduced and fat-modified (medium-chain triglyceride-supplemented) diet. Many patients still suffer acute life-threatening events or long-term neuropathic symptoms despite adequate treatment, and newborn screening has not significantly changed the prognosis for these severe phenotypes. Very long-chain acyl-CoA dehydrogenase deficiency recognized in neonatal screening, in contrast, frequently has a less severe disease course and dietary restrictions in many patients may be loosened. On the basis of the collected data, recommendations are given with regard to the fat and carbohydrate content of the diet, the maximal length of fasting periods and the use of l-carnitine in long-chain fatty acid oxidation defects.
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PMID:Treatment recommendations in long-chain fatty acid oxidation defects: consensus from a workshop. 1945 63

The world of metabolic myopathies has been dramatically modified by the advent of enzyme replacement therapy (ERT), the first causative treatment for glycogenosis type II (GSDII) or Pompe disease, which has given new impetus to research into that disease and also other pathologies. This article reviews new advances in the treatment of GSDII, the consensus about ERT, and its limitations. In addition, the most recent knowledge regarding the pathophysiology, phenotype, and genotype of the disease is discussed. Pharmacological, immunotherapy, nutritional, and physical/rehabilitative treatments for late-onset Pompe disease and other metabolic myopathies are covered, including treatments for defects in glycogen metabolism, such as glycogenosis type V (McArdle disease), and glycogenosis type III (debrancher enzyme deficiency), and defects in lipid metabolism, such as carnitine palmitoyltransferase II deficiency and electron transferring flavoprotein dehydrogenase deficiency, or riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency.
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PMID:Therapeutic advances in the management of Pompe disease and other metabolic myopathies. 2399 16

Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.
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PMID:Spectrum of metabolic myopathies. 2499 54