Introduction and background - LC-FAOD

Long-chain Fatty acid oxidation disorders (LC-FAOD) are inherited disorders of the mitochondrial fatty acid oxidation pathway with an abnormal response to fasting in the face of increased energy demands. This can result in fasting hypoglycaemia and an inappropriate accumulation of intermediate metabolites of fatty acid oxidation.

Fatty acids are broken down through mitochondrial ɞ-oxidation, which process is characterized by several hypoketotic hypoglycemia and sudden death in the neonatal period or early childhood.
Older children or adults may present with exercise or illness-induced rhabdomyolysis, but patients can remain asymptomatic throughout life as well.

The clinical problems in a defect in fatty acid oxidation result from the failure of the production of energy and accumulation of toxic intermediates. The defects in the oxidation of long and very long chain fatty acids result in hypoglycemia and encephalopathy, cardiomyopathy, and rhabdomyolysis¹.

Mitochondrial fatty acid oxidation involves 4 processes¹

Entry of fatty acids into mitochondria
Mitochondrial ɞ-oxidation using membrane bound enzymes
Mitochondrial ɞ-oxidation using chain shortened fatty acids using matrix enzymes
Electron transfer to the respiratory chain

The clinical presentation of these disorders is heterogeneous.
The management of some of these disorders consists of primarily dietary management.

New born screening greatly reduced morbidity and mortality, but does not prevent neonatal death in some severe phenotypes. The dietary management should be tailored towards the severity of the phenotype and the specific disorder.¹

The spectrum of FAOD differs widely between etnic groups.
Incidence calculations from reports from Australia, Germany, and the US provide a combined incidence of 1:9300 with a much lower incidence in Asians.³

References

Spiekerkoetter U, Duran M. Mitochondrial Fatty Acid Oxidation Disorders. In: Physician’s guide to the diagnosis, treatment and follow up of Inherited Metabolic Diseases 2^nd ed: Blau N. Springer Heidelberg New York 2014:247-266
Roe CR. Ding J. Mitochondrial fatty acid oxidation disorders. In: Scriver CR et al. ed. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw Hill, 2001:2297-2326.
Lindner M, Hoffmann GF et al. Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting. J Inher Metab Dis, 2010;33:521-526)

The products mentioned within the material are classified as Foods for Special Medical Purposes (FSMPs), intended for patients who have been medically diagnosed and must be under medical supervision.