Fatty acid oxidation defects as a cause of neuromyopathic disease in infants and adults.
Fatty acids are a major fuel for the body and fatty acid oxidation is particularly important during fasting, sustained aerobic exercise & stress. The myocardium and resting skeletal muscle utilise long-chain fatty acids as a major source of energy. Inherited disorders of fatty acid oxidation seriously compromise the function of muscle and other highly energy-dependent tissues such as brain, nerve, heart, kidney & liver. Defects of fatty acid oxidation lead to a range of neuromyopathic disease in both adults and children. Such defects encompass a wide spectrum of clinical disease, presenting in the neonatal period or infancy with recurrent hypoketotic hypoglycaemic encephalopathy, liver dysfunction and hyperammonaemia with neurosensory deficits secondary to the acute onset. In addition, there may be cardiac arrhythmias and/or progressive cardiomyopathy, which may give rise to secondary hypoxic-ischaemic encephalopathy. In older children, adolescence or adults there is often exercise intolerance with episodic myalgia or rhabdomyolysis in association with prolonged aerobic exercise or other exacerbating factors. Some disorders are particularly associated with toxic metabolites that may contribute to encephalopathy, polyneuropathy, axonopathy and pigmentary retinopathy. Diagnosis is through clinical suspicion with appropriate investigations in blood and urine taken during crisis. Definitive diagnosis is usually by fibroblast assay. Treatment is generally through avoidance of fasting, frequent carbohydrate rich feeds and in long-chain defects MCT supplementation. Novel treatments include the use of D,L-3-hydroxybutyrate and the potential use of fibrates to increase mutant protein levels in mild disorders.
Department of Clinical Chemistry, Sheffield Children's Hospital, Sheffield, S10 2TH, UK.
Simon E
SE
Olpin
D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency; D001928:Brain Diseases, Metabolic / Q000209:etiology* / Q000628:therapy; D002331:Carnitine / Q000096:biosynthesis / Q000172:deficiency; D004035:Diet Therapy; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D024101:Mitochondrial Proteins / Q000172:deficiency; D010084:Oxidation-Reduction
D005227:Fatty Acids; D024101:Mitochondrial Proteins; D042964:Acyl-CoA Dehydrogenase; D002331:Carnitine