Fetal Fatty Acid Oxidation Disorders, Their Effect on Maternal Health and Neonatal Outcome: Impact of Expanded Newborn Screening on Their Diagnosis and Management

摘要

Mitochondrial fatty acid oxidation disorders (FAOD) are recessively inherited errors of metabolism. Newborns with FAOD typically present with hypoketotic hypoglycemia, metabolic acidosis, hepatic failure, and cardiomyopathy. Late presentations include episodic myopathy, neuropathy, retinopathy, and arrhythmias. Sudden unexpected death can occur at any age and can be confused with sudden infant death syndrome. Some FAOD are associated with intrauterine growth restriction, prematurity, and pregnancy complications in the heterozygous mother, such as severe preeclampsia, acute fatty liver of pregnancy (AFLP), or hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Maternal pregnancy complications occur primarily in mothers carrying a fetus with long-chain l-3-hydroxyacyl CoA dehydrogenase deficiency or general trifunctional protein deficiencies. FAOD as a group represent the most common inborn errors of metabolism, and presymptomatic diagnosis of FAOD is the key to reduce morbidity and avoid mortality. The application of tandem mass spectrometry to newborn screening provides an effective means to identify most FAOD patients presymptomatically. At the beginning of 2005, 36 state newborn screening programs have mandated or adopted this technology resulting in a marked increase in the number of asymptomatic neonates with FAOD diagnosed. To ensure the long-term benefits of such screening programs, pediatricians and other health care providers must be educated about these disorders and their treatment.Abbreviations: AFLP, acute fatty liver of pregnancy; FAO, fatty acid oxidation; FAOD, fatty acid oxidation disorders; HELLP, hemolysis, elevated liver enzymes, and low platelets syndrome; HMGCL, 3-hydroxy-3-methylglutaryl-CoA lyase; HMGCS2, 3-hydroxy-3-methylglutaryl-CoA synthetase; LCAD, long-chain acyl CoA dehydrogenase; LCHAD, long-chain l-3-hydroxyacyl CoA dehydrogenase; LKAT, long-chain 3-ketoacyl-CoA thiolase; MCAD, medium-chain acyl CoA dehydrogenase; MS/MS, tandem mass spectrometry; MTP, mitochondrial trifunctional protein; OA, organic acidemias; SCHAD, short-chain l-3-hydroxyacyl CoA dehydrogenase; SIDS, sudden infant death syndrome; VLCAD, very-long-chain acyl CoA dehydrogenase