Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A severe fatty acid oxidation disorder

Abstract Three patients presented with evidence of a fatty acid oxidation disorder. Analysis of urinary organic acids by gas chromatography/mass spectrometry demonstrated the presence of medium-chain (C6-C12) dicarboxylic, 3-hydroxydicarboxylic, and 3-ketodicarboxylic acids in all three urines. 3-Ketodicarboxylic aciduria is reported for the first time here, as are the mass spectra for 3-ketosuberic, 3-ketosebacic, and 3-ketododecanedioic acids and the oximated spectrum for 3-ketoadipic acid. The presence of 3-ketodicarboxylic acids suggests a defect at the level of a long-chain 3-ketoacyl-CoA thiolase, an enzyme for which a deficiency state has not previously been described. Our patients may represent the first cases of a long-chain thiolase defect.

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

PEDIATRICS ◽

10.1542/peds.87.3.328 ◽

1991 ◽

Vol 87 (3) ◽

pp. 328-333 ◽

Cited By ~ 1

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.

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Round Table Discussion

Annals of Nutrition and Metabolism ◽

10.1159/000448323 ◽

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).

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

Orvosi Hetilap ◽

10.1556/650.2017.30923 ◽

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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Fibroblast Fatty-Acid Oxidation Flux Assays Stratify Risk in Newborns with Presumptive-Positive Results on Screening for Very-Long Chain Acyl-CoA Dehydrogenase Deficiency

International Journal of Neonatal Screening ◽

10.3390/ijns3010002 ◽

2017 ◽

Vol 3 (1) ◽

pp. 2 ◽

Cited By ~ 4

Author(s):

Simon Olpin ◽

Shirley Clark ◽

Jane Dalley ◽

Brage Andresen ◽

Joanne Croft ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

Dehydrogenase Deficiency ◽

Acid Oxidation ◽

Chain Acyl ◽

Positive Results ◽

Long Chain

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Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with hyperinsulinism: a novel glucose–fatty acid cycle?

Biochemical Society Transactions ◽

10.1042/bst0311137 ◽

2003 ◽

Vol 31 (6) ◽

pp. 1137-1139 ◽

Cited By ~ 35

Author(s):

S. Eaton ◽

I. Chatziandreou ◽

S. Krywawych ◽

S. Pen ◽

P.T. Clayton ◽

...

Keyword(s):

Insulin Secretion ◽

Fatty Acid ◽

Fatty Acid Oxidation ◽

Dehydrogenase Deficiency ◽

Short Chain ◽

Acid Oxidation ◽

Β Cells ◽

Molecular Defects ◽

Glucose Fatty Acid Cycle ◽

Hydroxyacyl Coa Dehydrogenase

Hyperinsulinism of infancy is caused by inappropriate insulin secretion in pancreatic β-cells, even when blood glucose is low. Several molecular defects are known to cause hyperinsulinism of infancy, such as KATP channelopathies and regulatory defects of glucokinase and glutamate dehydrogenase. Although defects of fatty acid oxidation have not previously been known to cause hyperinsulinism, patients with deficiency in SCHAD (short-chain 3-hydroxyacyl-CoA dehydrogenase; an enzyme of mitochondrial β-oxidation) have hyperinsulinism. A novel link between fatty acid oxidation and insulin secretion may explain hyperinsulinism in these patients.

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