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Published in:

01-07-2013 | SSIEM Symposium 2012

Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability

Author: Simon E Olpin

Published in: Journal of Inherited Metabolic Disease | Issue 4/2013

Abstract

Fatty acids are a major fuel for the body and fatty acid oxidation is particularly important during fasting, sustained aerobic exercise and stress. The myocardium and resting skeletal muscle utilise long-chain fatty acids as a major source of energy. Inherited disorders affecting fatty acid oxidation seriously compromise the function of muscle and other highly energy-dependent tissues such as brain, nerve, heart, kidney and liver. Such defects encompass a wide spectrum of clinical disease, presenting in the neonatal period or infancy with recurrent hypoketotic hypoglycaemic encephalopathy, liver dysfunction, hyperammonaemia and often cardiac dysfunction. 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. The phenotypic diversity encountered in defects of fat oxidation is partly explained by genotype/phenotype correlation and certain identifiable environmental factors but there remain many unresolved questions regarding the complex interaction of genetic, epigenetic and environmental influences that dictate phenotypic expression. It is becoming increasingly clear that the view that most inherited disorders are purely monogenic diseases is a naive concept. In the future our approach to understanding the phenotypic diversity and management of patients will be more realistically achieved from a polygenic perspective.

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Title: Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability
Author: Simon E Olpin
Publication date: 01-07-2013
Publisher: Springer Netherlands
Published in: Journal of Inherited Metabolic Disease / Issue 4/2013
Print ISSN: 0141-8955
Electronic ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-013-9611-5

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