Very long chain acyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts

1993 ◽  
Vol 1180 (3) ◽  
pp. 327-329 ◽  
Author(s):  
Catherine Bertrand ◽  
Claude Largillière ◽  
Marie Thérèse Zabot ◽  
Monique Mathieu ◽  
Christine Vianey-Saban
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Inborn Error ◽  
Dehydrogenase Deficiency ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Chain Acyl ◽  
Long Chain

scholarly journals Medium-Chain Acyl-CoA Dehydrogenase Deficiency in an Infant with Dilated Cardiomyopathy

2009 ◽  
Vol 2009 ◽  
pp. 1-3 ◽  
Author(s):  
Marcello Marcì ◽  
Patrizia Ajovalasit
Keyword(s):  
Fatty Acid ◽  
Dilated Cardiomyopathy ◽  
Dehydrogenase Deficiency ◽  
Acid Oxidation ◽  
Inherited Disorders ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Medium Chain ◽  
Mitochondrial Fatty Acid ◽  
Chain Acyl ◽  
Long Chain

We report about an infant affected by dilated cardiomyopathy (CMP) in whom metabolic investigations evidenced medium-chain-acyl-CoA dehydrogenase deficiency (MCADD), that is one of three types of inherited disorders of mitochondrial fatty-acid -oxidation. Long-chain and very long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficits are recognized as responsible of hypertrophic or, less frequently, dilated cardiomyopathy (CMP) in childhood. Otherwise, to our knowledge, no case of MCADD associated to dilated CMP has been reported in literature.

scholarly journals Nrf2 affects the efficiency of mitochondrial fatty acid oxidation

2014 ◽  
Vol 457 (3) ◽  
pp. 415-424 ◽  
Author(s):  
Marthe H. R. Ludtmann ◽  
Plamena R. Angelova ◽  
Ying Zhang ◽  
Andrey Y. Abramov ◽  
Albena T. Dinkova-Kostova
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Saturated Fatty Acids ◽  
Acid Oxidation ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Atp Production ◽  
Mitochondrial Fatty Acid ◽  
Mitochondrial Oxidation ◽  
Long Chain

Transcription factor Nrf2 affects fatty acid oxidation; the mitochondrial oxidation of long-chain (palmitic) and short-chain (hexanoic) saturated fatty acids is depressed in the absence of Nrf2 and accelerated when Nrf2 is constitutively activated, affecting ATP production and FADH2 utilization.

Medium- and Short-Chain L-3-Hydroxyl-Acetyl-Coenzyme A Deficiency: A New Identified Mutation in Four Cases

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S9-S9
Author(s):  
Sheng Feng ◽  
Deborah Cooper ◽  
Lu Tan ◽  
Gail Meyers ◽  
Michael Bennett
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Coenzyme A ◽  
Short Chain ◽  
Acid Oxidation ◽  
Sequencing Analysis ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Chain Acyl ◽  
Unusual Phenotype

Abstract Medium- and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase (M/SCHAD, SCHAD) deficiency is a mitochondrial fatty acid oxidation disorder (FAOD). This enzyme catalyzes the penultimate step in fatty acid oxidation, the NAD+ dependent conversion of L-3-hydroxyacyl-CoA to 3-ketoacyl-CoA for medium- and short-chain acyl-CoA intermediates (C4-C12). The clinical presentations of most patients are recurrent hypoglycemia associated with hyperinsulinism. We presented four infants with C4 acyl-carnitine elevation identified by newborn screening that also showed an unusual phenotype of congenital hypotonia and gross developmental delay. Enzymatic studies confirmed the disease. Sequencing analysis of all the HADH coding exons on the four patients revealed a homozygous variant of a novel change (c.908G>T, p.Gly303Val). Western blot analysis subsequently confirmed the lack of the SCHAD protein. In addition, there is another previously reported benign variant (c.257T>C) identified in three infants. Therefore, we postulate that the HADH variant (c.908G>T) is indeed pathogenic and associated with a severe phenotype as evidenced by the cases described herein. Population screening for the c.908G>T mutation suggests this mutation to be common among Puerto Ricans. We recommend that SCHAD deficiency is included as part of the differential diagnosis of all infants with congenital hypotonia.

Hypoglycemia, Hypotonia, and Cardiomyopathy: The Evolving Clinical Picture of Long-Chain Acyl-CoA Dehydrogenase Deficiency

PEDIATRICS ◽  
1991 ◽  
Vol 87 (3) ◽  
pp. 328-333 ◽  
Author(s):  
William R. Treem ◽  
Jeffrey S. Hyams ◽  
Charles A. Stanley ◽  
Daniel E. Hale ◽  
Harris B. Leopold
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Dehydrogenase Deficiency ◽  
Response To Treatment ◽  
Acid Oxidation ◽  
Medium Chain ◽  
Chain Acyl ◽  
History Of ◽  
Related Enzyme ◽  
Long Chain

Inherited defects in fatty acid oxidation, which have been described and diagnosed with increasing frequency in the last decade, are most commonly attributed to a deficiency in the activity of medium-chain acyl-CoA dehydrogenase. Few cases of the related enzyme defect of long-chain acyl-CoA dehydrogenase activity have been reported. An infant with documented long-chain acyl-CoA dehydrogenase deficiency is described with a detailed metabolic profile, long-term clinical follow-up, and response to treatment. This patient is compared with the seven previously published cases of this disorder in order to stress the unique features of the initial presentation, more subtle late manifestations of the disease, and clinical and biochemical differentiation from the more common medium-chain acyl-CoA dehydrogenase deficiency. This report stresses the enlarging spectrum of the clinical presentation and natural history of this defect in fatty acid oxidation.

scholarly journals Specific inhibition of mitochondrial fatty acid oxidation by 2-bromopalmitate and its co-enzyme A and carnitine esters

1972 ◽  
Vol 129 (1) ◽  
pp. 55-65 ◽  
Author(s):  
J. F. A. Chase ◽  
P. K. Tubbs
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Liver Mitochondria ◽  
Carnitine Palmitoyltransferase ◽  
Acid Oxidation ◽  
Dependent Manner ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Succinate Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Long Chain

1. The CoA and carnitine esters of 2-bromopalmitate are extremely powerful and specific inhibitors of mitochondrial fatty acid oxidation. 2. 2-Bromopalmitoyl-CoA, added as such or formed from 2-bromopalmitate, inhibits the carnitine-dependent oxidation of palmitate or palmitoyl-CoA, but not the oxidation of palmitoylcarnitine, by intact liver mitochondria. 3. 2-Bromopalmitoylcarnitine inhibits the oxidation of palmitoylcarnitine as well as that of palmitate or palmitoyl-CoA. It has no effect on succinate oxidation, but inhibits that of pyruvate, 2-oxoglutarate or hexanoate; however, the oxidation of these substrates (but not of palmitate, palmitoyl-CoA or palmitoyl-carnitine) is restored by carnitine. 4. In damaged mitochondria, added 2-bromopalmitoyl-CoA does inhibit palmitoylcarnitine oxidation; pyruvate oxidation is unaffected by the inhibitor alone, but is impaired if palmitoylcarnitine is subsequently added. 5. The findings have been interpreted as follows. 2-Bromopalmitoyl-CoA inactivates (in a carnitine-dependent manner) a pool of carnitine palmitoyltransferase which is accessible to external acyl-CoA. This results in inhibition of palmitate or palmitoyl-CoA oxidation. A second pool of carnitine palmitoyltransferase, inaccessible to added acyl-CoA in intact mitochondria, can generate bromopalmitoyl-CoA within the matrix from external 2-bromopalmitoylcarnitine; this reaction is reversible. Such internal 2-bromopalmitoyl-CoA inactivates long-chain β-oxidation (as does added 2-bromopalmitoyl-CoA if the mitochondria are damaged) and its formation also sequesters intramitochondrial CoA. Since this CoA is shared by pyruvate and 2-oxoglutarate dehydrogenases, the oxidation of their substrates is depressed by 2-bromopalmitoylcarnitine, unless free carnitine is available to act as a ‘sink’ for long-chain acyl groups. 6. These effects are compared with those reported for other inhibitors of fatty acid oxidation.

Round Table Discussion

2016 ◽  
Vol 68 (Suppl. 3) ◽  
pp. 21-23
Author(s):  
Susan Winter ◽  
Neil R.M. Buist ◽  
Nicola Longo ◽  
Saro H. Armenian ◽  
Gary Lopaschuk ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Dehydrogenase Deficiency ◽  
Round Table ◽  
Acid Oxidation ◽  
Round Table Discussion ◽  
Table Discussion ◽  
Chain Acyl ◽  
Acyl Coenzyme A ◽  
Long Chain

The 1st International Carnitine Working Group concluded with a round table discussion addressing several areas of relevance. These included the design of future studies that could increase the amount of evidence-based data about the role of carnitine in the treatment of fatty acid oxidation defects, for which substantial controversy still exists. There was general consensus that future trials on the effect of carnitine in disorders of fatty acid oxidation should be randomized, double-blinded, multicentered and minimally include the following diagnoses: medium-chain acyl coenzyme A (CoA) dehydrogenase deficiency, very long-chain acyl-CoA dehydrogenase deficiency, long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and mitochondrial trifunctional protein deficiency. Another area that generated interest was trials of carnitine in cardiomyopathy and, especially, the use of biomarkers to identify patients at greater risk of cardiotoxicity following treatment with anthracyclines. The possibility that carnitine treatment may lead to improvements in autistic behaviors was also discussed, although the evidence is still not sufficient to make any firm conclusions in this regard. Preliminary data on carnitine levels in children and adolescents with primary hypertension, low birth weight and nephrotic syndrome was also presented. Lastly, the panelists stressed that there remains an objective need to harmonize the terminology used to describe carnitine deficiencies (e.g., primary, secondary and systemic deficiency).

scholarly journals Inhibition by acetyl-CoA of hepatic carnitine acyltransferase and fatty acid oxidation

1983 ◽  
Vol 216 (2) ◽  
pp. 499-502 ◽  
Author(s):  
K McCormick ◽  
V J Notar-Francesco ◽  
K Sriwatanakul
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Acid Oxidation ◽  
Acetyl Coa ◽  
Mitochondrial Fatty Acid Oxidation ◽  
Acyltransferase Activity ◽  
Carnitine Acyltransferase ◽  
Mitochondrial Transfer ◽  
Mitochondrial Fatty Acid ◽  
Chain Acyl

At micromolar concentrations, acetyl-CoA inhibited hepatic carnitine acyltransferase activity and mitochondrial fatty acid oxidation. The inhibitory effects were not nearly as potent on a molar basis as those of malonyl-CoA; nevertheless, the cytosolic concentrations of acetyl-CoA, as yet unknown, may be sufficient (greater than 30 microM) to curtail appreciably the mitochondrial transfer of long-chain acyl-CoA units and fatty acid oxidation. Hence acetyl-CoA may also partially regulate hepatic ketogenesis.

scholarly journals Rhabdomyolysis – Mikor vessük fel metabolikus myopathia lehetőségét? Esetismertetés és diagnosztikus algoritmus

2017 ◽  
Vol 158 (47) ◽  
pp. 1873-1882
Author(s):  
Ágnes Sebők ◽  
Endre Pál ◽  
Gergő Attila Molnár ◽  
István Wittmann ◽  
Judit Berenténé Bene ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Dehydrogenase Deficiency ◽  
Acid Oxidation ◽  
Fatty Acid Oxidation Disorders ◽  
Metabolic Myopathies ◽  
Chain Acyl ◽  
Recurrent Rhabdomyolysis ◽  
Acyl Coenzyme A ◽  
Long Chain

Abstract: We report the case of a 46-year-old female patient with recurrent rhabdomyolysis. In the background of her metabolic myopathy an inherited metabolic disorder of the fatty acid oxidation, very long-chain acyl-coenzyme A-dehydrogenase deficiency was diagnosed. The diagnosis was based on abnormal acyl-carnitine- and urine organic-acid profile in addition to low residual enzyme activity, and was confirmed by genetic testing. After introduction of dietotherapy metabolic crisis necessitating hospital admission has not occurred neither have fixed myopathic changes developed. We present here the differential diagnosis of rhabdomyolysis and exertional muscle complaints, with the metabolic myopathies in focus. The main features of fatty acid oxidation disorders are highlighted, acute and chronic managements of very long-chain acyl-coenzyme A-dehydrogenase deficiency are discussed. Metabolic myopathies respond well to treatment, so good quality of life can be achieved. However, especially in fatty acid oxidation disorders, a metabolic crisis may develop quickly and can be fatal, albeit rarely. Some of these disorders can be identified by newborn screening, but occasionally the symptoms may manifest only in adulthood. With the presentation of this case we would like to point out that in the differential diagnosis of recurrent rhabdomyolysis inherited metabolic disorders should be considered regardless of the patient’s age. Orv Hetil. 2017; 158(46): 1873–1882.

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