Acylcoenzyme A dehydrogenase deficiency in heart tissue from infants who died unexpectedly with fatty change in the liver

Allison, F.; Bennett, Michael J.; Variend, S.; Engel, Peter

doi:10.1136/bmj.296.6614.11

Cited by 32 publications

(14 citation statements)

References 6 publications

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“…We investigated this method by immunoblotting using anti-human VLCAD antibody. About 20 and 80% of VLCAD protein were distributed to the supernatant and membrane fractions, respectively, suggesting that it is possible to identify VLCAD deficiency by measuring palmitoyl-CoA dehydrogenation activity in membrane fraction; in contrast, it may be hard to identify isolated LCAD deficiency by measuring this activity in supernatant fraction containing significant amounts of contaminating VLCAD.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.

Aoyama¹,

Souri²,

Ushikubo³

et al. 1995

J. Clin. Invest.

171

131

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Mitochondrial very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) was purified from human liver. The molecular masses of the native enzyme and the subunit were estimated to be 154 and 70 kD, respectively. The enzyme was found to catalyze the major part of mitochondrial palmitoylcoenzyme A dehydrogenation in liver, heart, skeletal muscle, and skin fibroblasts (89-97, 86-99, 96-99, and 78-87%, respectively).Skin fibroblasts from 26 patients suspected of having a disorder of mitochondrial a-oxidation were analyzed for VLCAD protein using immunoblotting, and 7 of them contained undetectable or trace levels of the enzyme. The seven deficient fibroblast lines were characterized by measuring acyl-coenzyme A dehydrogenation activities, overall palmitic acid oxidation, and VLCAD protein synthesis using pulse-chase, further confirming the diagnosis of VLCAD deficiency. These results suggested the heterogenous nature of the mutations causing the deficiency in the seven patients.Clinically, all patients with VLCAD deficiency exhibited cardiac disease. At least four of them presented with hypertrophic cardiomyopathy. This frequency (> 57%) was much higher than that observed in patients with other disorders of mitochondrial long-chain fatty acid oxidation that may be accompanied by cardiac disease in infants. (J. Clin. Invest. 1995Invest. . 95:2465Invest. -2473

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Section: Resultsmentioning

confidence: 99%

“…In contrast to MCAD deficiency, other defects, such as short-chain acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase (LCAD) deficiencies, are rare. The detailed clinical descriptions of these defects are quite variable, and many patients die before 1 yr of age (12)(13)(14)(15)(16)(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.

Aoyama¹,

Souri²,

Ushikubo³

et al. 1995

J. Clin. Invest.

171

131

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show abstract

“…Lanes 1 and 2, 100 and 10 ng, respectively, of purified rat MCAD were directly applied as standard; lanes 3 and 4, 133 ng of rat MCAD after preabsorption with preimmune rabbit serum and anti-LCAD antibody, respectively; lanes 5 and 6, 13.3 ng of rat MCAD after preabsorption with preimmune rabbit serum and anti-LCAD antibody, respectively. The intense bands above the MCAD bands (lanes [3][4][5][6] are the heavy chain of IgG derived from the preimmune serum or the antibodies used. The broad, faint bands seen in each lane are a result of BSA being used as a camer.…”

Section: Characterization Of Interactions Of Rat and Human L C A D Andmentioning

confidence: 99%

“…Heterogeneity of LCAD deficiency was also suggested by a biochemical assay (3). As in the case of MCAD deficiency (4), some patients with LCAD deficiency abruptly died with few prodromal symptoms, mimicking sudden infant death syndrome (5). No urinary metabolites are specific for this disease, making it difficult to establish the diagnosis.…”

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confidence: 99%

Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency

et al. 1991

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ABSTRACT. Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is a disorder of mitochondria1 fatty acid oxidation that is characterized by hypoglycemia, muscle weakness, and hepato-and cardiomegaly. To characterize variant LCAD, we first carried out preliminary experiments using pure enzyme preparations. Despite the significant sequence similarity of LCAD to medium-chain acylCoA dehydrogenase, the antibody raised against rat LCAD was monospecific for human and rat LCAD and did not cross-react with either human or rat medium-chain acylCoA dehydrogenase. Immunoblot analysis of variant LCAD in cultured fibroblasts from nine patients with LCAD deficiency revealed a single LCAD band in all nine LCAD-deficient cell lines. Each variant LCAD was comparable in molecular size and quantity to normal LCAD, suggesting that the LCAD mutation in each of these cell lines is likely to be a point mutation that produces a stable variant LCAD. The uniform nature of variant LCAD suggests that only a single, or at most a few, prevalent point mutations may be found in the majority of LCAD-deficient patients. If this is the case, it should be possible to devise a molecular diagnostic method for LCAD deficiency. (Pediatr Res 30: [211][212][213][214][215] 1991) Abbreviations LCAD, long-chain acyl-CoA dehydrogenase MCAD, medium-chain acyl-CoA dehydrogenase SCAD, short-chain acyl-CoA dehydrogenase LCAD deficiency is an autosomal recessive disorder of fatty acid metabolism. It was first described in three infants in 1985 by Hale et al. (1). Subsequently, 1 1 additional patients have been identified (2). The main clinical features seen in these patients were severe hypoglycemia, skeletal muscle weakness, and hepatomegaly; cardiomegaly was a significant feature in eight patients. Six of them died in early infancy; however, the clinical manifestations in some other cases were much milder (1, 2), suggesting

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“…A retrospective study of material collected at autopsy from 200 consecutive sudden infant deaths identified 14 with severe diffuse microvesicular panlobular fatty infiltration of the liver. In nine cases sufficient stored material (liver or heart muscle) was available for specific enzyme assays, leading to the diagnosis of three cases of medium-chain and one of long-chain acyl-CoA dehydrogenase deficiency (Howat et al, 1985;Allison et al, 1988a). In two of the cases of medium-chain acyl-CoA dehydrogenase deficiency the diagnosis was confirmed by the subsequent birth of affected siblings while in the third case a small amount of urine, collected post-mortem, contained high concentrations of dicarboxylic acids as expected.…”

Section: Sudden Infant Deathmentioning

confidence: 99%

Disorders of mitochondrial β‐oxidation: Prenatal and early postnatal diagnosis and their relevance to Reye's syndrome and sudden infant death

Pollitt

1989

J of Inher Metab Disea

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There are still many problems with the diagnosis and classification of inherited disorders of mitochondrial beta-oxidation. At present only the acyl-CoA dehydrogenase step of the beta-oxidation spiral has been explored in any detail and a large number of patients have disorders that cannot be properly characterized. beta-Oxidation defects may present in a wide variety of ways, the most dramatic being acute encephalopathy with hepatic involvement (atypical Reye's syndrome) or 'sudden' death. Investigations may include urinary and plasma organic acids, metabolic stress tests and assays of overall metabolic pathways or of specific enzymes in cultured fibroblasts, lymphocytes, or other material. Early postnatal diagnosis presents particular difficulties but in medium-chain acyl-CoA dehydrogenase deficiency the diagnosis may be apparent from careful examination of urine. There is as yet little general experience in prenatal diagnosis of this group of disorders except for glutaric aciduria type II. Single prenatal diagnoses of medium-chain acyl-CoA dehydrogenase deficiency and of an incompletely characterized defect of medium-chain fatty acid oxidation have been performed.

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Acylcoenzyme A dehydrogenase deficiency in heart tissue from infants who died unexpectedly with fatty change in the liver

Cited by 32 publications

References 6 publications

Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.

Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients.

Immunochemical Characterization of Variant Long-Chain Acyl-CoA Dehydrogenase in Cultured Fibroblasts from Nine Patients with Long-Chain Acyl-CoA Dehydrogenase Deficiency

Disorders of mitochondrial β‐oxidation: Prenatal and early postnatal diagnosis and their relevance to Reye's syndrome and sudden infant death

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