Fatty Acid Oxidation Disorders


Mitochondrial fatty acid oxidation (FAO) is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress. A number of inherited disorders affecting this metabolic pathway have been known for almost two decades. Defects of mitochondrial FAO characteristically present with severe metabolic crises associated with low blood glucose (hypoglycaemia) during infancy and childhood and are also a relatively frequent cause of muscle diseases and cardiac muscle disease. The symptoms are typically episodic and often associated with mild viral infections or fasting. Therapeutic interventions are generally effective in preventing metabolic decompensation, which emphasizes the importance of early diagnosis. Diagnostic testing, determining optimal dietary regimens for each disorder and prenatal screening for these disorders may essentially alter an otherwise poor prognosis for many patients with FAO disorders.

Key Concepts:

  • Fatty acids can be oxidized by α‐oxidation in peroxisomes, by β‐oxidation in mitochondria and peroxisomes, and ω‐oxidation in the endoplasmic reticulum.

  • Mitochondrial FAO is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress.

  • A single β‐oxidation cycle consists of a series of four repeated enzymatic steps: dehydrogenation (oxidation), hydration, a second dehydrogenation and thiolytic cleavage of the carbon chain.

  • Mitochondrial FAO defects present with severe metabolic crises associated with nonketotic hypoglycaemia, fatty liver, muscle weakness and cardiomyopathy.

  • As a group, mitochondrial FAO defects are among the most common autosomal recessively inherited metabolic disorders.

  • The main objective of therapeutic intervention is to secure sufficient caloric intake during periods of metabolic stress and fasting, and prevent accumulation of β‐oxidation intermediates.

  • Neonatal screening of FAO disorders has been initiated in several countries worldwide, improving the opportunities for early dietary therapies.

Keywords: fatty acid oxidation; β‐oxidation; inherited metabolic defects; mitochondria

Figure 1.

Mitochondrial fatty acid β‐oxidation pathway.



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Further Reading

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Spiekerkoetter U, Lindner M, Santer R et al. (2009) Management and outcome in 75 individuals with long‐chain fatty acid oxidation defects: results from a workshop. Journal of Inherited Metabolic Disease.

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Polinati, Padmini P, Eskelin, Petra, and Tyni, Tiina(Dec 2009) Fatty Acid Oxidation Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003067.pub2]