Defects of fatty-acid oxidation in muscle.
Long-chain fatty acids (LCFA) are oxidized by muscle mitochondria after transport in the cytosol by fatty-acid-binding protein(s) and their activation by a thiokinase. Carnitine, two forms of carnitine palmitoyltransferase(s) and carnitine acylcarnitine translocase are involved in LCFA gating. A primary genetic carnitine deficiency occurs in children with dilated cardiomyopathy, hypoglycaemia and low carnitine content in plasma, liver and muscle, owing to a defect in a common high-affinity transport system. This high-affinity transport in muscle differs from a low-affinity transport that has modifications during muscle maturation. The genetic enzyme defects of beta-oxidation (long-chain acyl-CoA dehydrogenase, medium- and short-chain acyl-CoA-dehydrogenase) present with Reye-like attacks that may lead to non-ketotic hypoglycaemia, coma and sudden infant death syndrome. There is elevated urinary excretion of dicarboxylic acids, acylcarnitines and acylglycines. Secondary carnitine deficiency may occur. ETF and ETF dehydrogenase deficiencies may present in a neonatal form with congenital anomalies, or in a later-onset form with ethylmalonic adipic aciduria. A still-unidentified defect leads to LCFA accumulation in fibroblasts, bone marrow, liver and muscle cells in a multisystem triglyceride disorder.
Angelini
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D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency; D000818:Animals; D002331:Carnitine / Q000172:deficiency; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency; D044927:Electron-Transferring Flavoproteins; D005227:Fatty Acids / Q000378:metabolism*; D005420:Flavoproteins / Q000378:metabolism; D006801:Humans; D007506:Iron-Sulfur Proteins; D008052:Lipid Metabolism, Inborn Errors; D009097:Multienzyme Complexes / Q000172:deficiency; D009132:Muscles / Q000378:metabolism*; D009135:Muscular Diseases / Q000209:etiology*; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors; D014280:Triglycerides / Q000378:metabolism
D044927:Electron-Transferring Flavoproteins; D005227:Fatty Acids; D005420:Flavoproteins; D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; D014280:Triglycerides; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine