Genetic Deficiency of Medium-Chain Acyl Coenzyme A Dehydrogenase: Studies in Cultured Skin Fibroblasts and Peripheral Mononuclear Leukocytes

Coates, Paul M.; Hale, Daniel E.; Stanley, Charles A.; Corkey, Barbara E.; Cortner, Jean A.

doi:10.1203/00006450-198507000-00007

Cited by 113 publications

(46 citation statements)

References 19 publications

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“…Many of the features of long-chain acyl CoA dehydrogenase deficiency are also seen in patients with the closely related disorder, medium-chain acyl CoA dehydrogenase deficiency (8,19). Common features include episodes of nonketotic coma that are provoked by fasting, secondary carnitine deficiency, and dicarboxylic aciduria.…”

Section: Discussionmentioning

confidence: 97%

Long-Chain Acyl Coenzyme A Dehydrogenase Deficiency: An Inherited Cause of Nonketotic Hypoglycemia

et al. 1985

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ABSTRACT. 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 mitochondria1 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, COz evolution from long-chain fatty acids was significantly reduced, while COz evolution from mediumchain and short-chain fatty acids was comparable to control values-findings consistent with a defect early in the /3- Vol. 19, No. 7, 1985 Printed in U.S.A.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. These results describe a previously unrecognized metabolic disorder of fatty acid oxidation due to a deficiency of the long-chain acyl CoA dehydrogenase which may present in early childhood with disastrous consequences. This diagnosis should be considered in children who present with nonketotic hypoglycemia, carnitine insufficiency, and inadequately explained cardiorespiratory arrests. (Pediatr Res 19: 666-671, 1985) Abbreviations CoA, coenzyme A ETF, electron transfer flavoprotein

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Section: Discussionmentioning

confidence: 97%

Long-Chain Acyl Coenzyme A Dehydrogenase Deficiency: An Inherited Cause of Nonketotic Hypoglycemia

et al. 1985

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“…Acyl-CoA dehydrogenase activity for palmitic, octanoic, and succinic CoA esters was carried out essentially as described by Coates et al (5). The activity of 3-hydroxyacyl-CoA dehydrogenase for acetoacetyl-CoA, 3-keto-octanoyl-CoA and 3-keto-hexadecanoyl-CoA and the activity of 3-ketoacyl-CoA thiolase were measured in homogenates of cultured fibroblasts as recently described (1 9).…”

Section: Methodsmentioning

confidence: 99%

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

et al. 1990

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ABSTRACT. A child presented in early childhood with episodes of coma and hypoglycemia and a rapidly evolutive myopathy and cardiomyopathy leading to death at 9 mo of age. Ketosis was decreased (blood P-hydroxybutyrate: 0.07 mmol/L) despite normal plasma levels of fatty acids (0.81 mmol/L). The patient's urine contained excessive amounts of the Cs to Clo dicarboxylic acids present in almost all defects of fatty acid mitochondrial oxidation. More specifically, gas chromatography-mass spectrometry identified an accumulation of medium-and long-chain (Cs to C14) 3-hydroxy-dicarboxylic acids, suggesting a defect of the mitochondrial enzyme that normally dehydrogenates these 3-hydroxyacyl-CoA esters. Biochemical studies in the patient's cultured fibroblasts confirmed the impairment of medium-and long-chain fatty acid oxidation, and allowed the recognition of the deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase. The activities of long-, medium-, and short-chain acyl-CoA dehydrogenases and 3-ketoacylCoA thiolase were normal. These results describe a disorder of fatty acid metabolism that affects the liver, skeletal muscles, and myocardium. It is important to point out that long-chain 3-hydroxyacyl-CoA deficiency shares many clinical similarities with systemic carnitine deficiency, as well as with carnitine-palmityl-CoA transferase and longchain acyl-CoA dehydrogenase deficiencies. The differential diagnosis of this disease relies on the demonstration of long-chain urinary dicarboxylic acids with a hydroxyl group in 3-position and the study of the enzyme activity in cultured fibroblasts. (Pediatr Res 28: 657-662, 1990)

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“…Fibroblast cultures from patients R-1 and K were assayed for long-, medium-, and short-chain acyl-coA dehydrogenase activity, using palmityl-coA, octanoyl-coA, and butyryl-coA respectively as the substrates. The assays were performed at the Children's Hospital, Philadelphia by Dr. P. Coates, using a method (23) …”

Section: Case Reportsmentioning

confidence: 99%

Diagnostic and Therapeutic Implications of Medium-Chain Acylcarnitines in the Medium-Chain Acyl-CoA Dehydrogenase Deficiency

et al. 1985

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Genetic Deficiency of Medium-Chain Acyl Coenzyme A Dehydrogenase: Studies in Cultured Skin Fibroblasts and Peripheral Mononuclear Leukocytes

Cited by 113 publications

References 19 publications

Long-Chain Acyl Coenzyme A Dehydrogenase Deficiency: An Inherited Cause of Nonketotic Hypoglycemia

Long-Chain Acyl Coenzyme A Dehydrogenase Deficiency: An Inherited Cause of Nonketotic Hypoglycemia

Deficiency of Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase: A Cause of Lethal Myopathy and Cardiomyopathy in Early Childhood

Diagnostic and Therapeutic Implications of Medium-Chain Acylcarnitines in the Medium-Chain Acyl-CoA Dehydrogenase Deficiency

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