Fatty acid oxidation disorders

Abstract

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism due to disruption of either mitochondrial β-oxidation or the fatty acid transport using the carnitine transport pathway. The presentation of a FAOD will depend upon the specific disorder, but common elements may be seen, and ultimately require a similar treatment. Initial presentations of the FAODs in the neonatal period with severe symptoms include cardiomyopathy, while during infancy and childhood liver dysfunction and hypoketotic hypoglycemia are common. Episodic rhabdomyolysis is frequently the initial presentation during or after adolescence; although, these symptoms may develop at any age for most of the FAODs The treatment of all FAOD's include avoidance of fasting, aggressive treatment during illness, and supplementation of carnitine, if necessary. The long-chain FAODs differ by requiring a fat-restricted diet and supplementation of medium chain triglyceride oil and often docosahexaenoic acid (DHA)-an essential fatty acid, crucial for brain, visual, and immune functions and prevention of fat soluble vitamin deficiencies. The FAOD are a group of autosomal recessive disorders associated with significant morbidity and mortality, but early diagnosis on newborn screening (NBS) and early initiation of treatment are improving outcomes. There is a need for clinical studies including randomized, controlled, therapeutic trials to continue to evaluate current understanding and to implement future therapies.

Clinical manifestations and management of fatty acid oxidation disorders

“…Prevalence [16] Acylcarnitine elevations [17] CPT-IAD CPT1A 1:750,000 to 1:2,000,000 C0, C0/(C16 + C18) ratio CACTD SLC25A20 C16, C16:1, C18 C0 free carnitine, CACTD carnitine-acylcarnitine translocase deficiency, CPT-IAD/CPT-IID carnitine palmitoyltransferase I/II deficiency, FAOD fatty acid oxidation disorder, LC-FAOD long-chain fatty acid oxidation disorders, LCHADD long-chain L-3 hydroxyacyl-CoA dehydrogenase deficiency, MCADD medium-chain acyl-CoA dehydrogenase deficiency, TFPD tri-functional protein deficiency, VLCADD very-long-chain acyl-CoA dehydrogenase deficiency before they were two years old, with approximately one-third first presenting as neonates [23]. A large proportion (46%) in this series presented with hypoketotic hypoglycemia; other symptoms reported in infants were coma triggered by fasting or catabolism, Reye Syndrome-like episodes, cardiomyopathy, and symptoms of acute myolysis [23].…”

“…The onset of peripheral neuropathy can vary based on underlying FAOD; however, it persists as a progressive presentation of the disease. As the neuropathy progresses, it can require more frequent clinical monitoring, although its treatment can be difficult [17]. Moreover, since this manifestation is irreversible, it poses a lifelong impact on patient QoL [46].…”

Metabolic Alterations in Inherited Cardiomyopathies

“…FA oxidation disorders (FAODs) include defects of metabolism caused by abnormalities in either mitochondrial β-oxidation or the import of FA in the mitochondrial matrix via the carnitine shuttle [199]. The former are determined by recessive mutations in genes encoding for the very long-chain acyl-CoA dehydrogenase (VLCAD), the long chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) and the trifunctional mitochondrial protein (TFP).…”

Recurrent Hypoglycemia in a Case of Congenital Analbuminemia

“…In this situation free fatty acid oxidation plays an important role for energy homeostasis. Disorders of free fatty acid metabolism are associated with occurrence of hypoglycemia [15]. Studies from analbuminemic rats have shown improved insulin sensitivity, increased insulin secretion, faster depletion of liver glycogen stores during fasting, free fatty acid deficiency with reduced rates of hepatic lipogenesis, triglyceride secretion, and limited lipoprotein lipase activity [4,5].…”