Disorders of fatty acid transport and mitochondrial oxidation: challenges and dilemmas of metabolic evaluation.

Abstract

Inborn errors of fatty acid transport and mitochondrial oxidation (FATMO) have drawn considerable attention in recent years for the rapid pace of discovery of new defects and an ever-increasing spectrum of clinical phenotypes. Several of these disorders are not detected by conventional biochemical investigations, even when a patient is symptomatic with fasting intolerance or functional failure of fatty acid dependent tissue(s). In our view, today's major challenges are the inclusion of FATMO disorders in newborn screening programs and the investigation of the role played by individual disorders in maternal complications of pregnancy, sudden and unexpected death in early life, and pediatric acute/fulminant liver failure. Dilemmas are found in the debate over the limitations, if any, to be imposed on the expansion of newborn screening using tandem mass spectrometry, in the provision of prenatal diagnosis for otherwise treatable disorders, and in the diagnostic workup of "unclassified" cases.