Genetic disorders of mitochondrial fatty acid oxidation

Abstract

Genetic diseases of mitochondrial fatty acid oxidation have recently emerged as important disorders to consider in the differential diagnosis of hypoglycemia, cardiomyopathy, or skeletal muscle weakness in infants and children. A total of 16 different defects have been identified over the past decade that involve almost all of the possible enzyme steps in the pathway. One of these disorders, medium-chain acyl-coenzyme A dehydrogenase deficiency has a frequency as high as 1 in 10,000 births and is the single most common genetic defect of intermediary metabolism. The disorders are frequently mistaken for Reye syndrome or sudden infant death syndrome. Improved methods have simplified the diagnosis of some of the fatty acid oxidation defects. However, recognition of these disorders remains challenging. Rapid advances have continued to be made over the past year in defining clinical phenotypes, diagnostic methods, and therapeutic strategies. Familiarity with this new group of disorders is becoming increasingly important for general pediatricians as well as subspecialists in metabolism, endocrinology, gastroenterology, cardiology, neurology, and genetics.