Fatty Acid Oxidation Disorders: An Update

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism caused by genetic variants which lead to disruption of the beta oxidation of fatty acids. The underlying pathogenetic mechanism is either a defect in an enzyme of the beta oxidation cycle or a defect in carnitine transport, which results in energy deficiency. FAODs have a wide spectrum of clinical presentations with variable age of onset of symptoms. The most common presentation is an acute Reye syndrome-like condition associated with hypoketotic hypoglycemia and liver dysfunction, which can lead to seizures, coma, and death. Newborn metabolic screening and availability of molecular genetic tests have significantly added to early and accurate diagnosis of these disorders. However, symptomatology can be non-specific and of sudden onset precipitated by intercurrent illness and may sometimes be overlooked in the absence of a high index of suspicion. Hence, they are associated with significant mortality and morbidity. Early diagnosis and management are crucial to improve the outcomes in affected patients. This paper provides an overview of the etiopathogenesis, clinical presentations, diagnosis and management of fatty acid oxidation defects, including current diagnostic modalities and recent therapeutic advances.