J Vockley1. 1. Department of Medical Genetics, Mayo Clinic Rochester, MN 55905.
Abstract
OBJECTIVE: To review the current understanding of the rapidly changing field of disorders of fatty acid metabolism and to discuss the future directions for research. DESIGN: A literature review of the basic biochemistry of the beta-oxidation pathway and clinical cases of defects of fatty acid metabolism are presented, and the diagnosis and treatment of such defects are discussed. MATERIAL AND METHODS: In many cases, a correct diagnosis will be made only if these disorders are specifically considered and appropriate tests are obtained, because results of screening tests for other organic acidemias are often normal in these entities. RESULTS: The first disorder of fatty acid metabolism was described only 20 years ago. Since then, at least 15 different inborn errors of metabolism that affect beta-oxidation have been identified, most in the past 10 years. Within the past 5 years, investigators have realized that a deficiency of one of these enzymes, medium-chain acyl coenzyme A dehydrogenase, may be one of the most common inborn errors of metabolism. This disorder may have a frequency equal to that of phenylketonuria in some populations in the United States and northern Europe. Approximately 1 to 3% of all unexplained deaths during infancy and childhood are probably related to disorders of beta-oxidation. Diagnosis of these disorders can be difficult because of the intermittent nature of the excretion of characteristic compounds. The mainstay of therapy for defects of beta-oxidation is avoidance of fasting. CONCLUSION: All patients with a suspected defect of fatty acid metabolism should be assessed and monitored by a specialist trained in the care of such patients. Continued improvements in the ability to diagnose and treat these disorders will be directly linked to new advances in the basic research on these enzymes. Movements to screen newborns for medium-chain acyl coenzyme A dehydrogenase are under way in some medical centers. Proposed tests include metabolite analysis or direct mutation analysis (or both) from blood spots from newborn screening cards already obtained for every newborn in the United States.
OBJECTIVE: To review the current understanding of the rapidly changing field of disorders of fatty acid metabolism and to discuss the future directions for research. DESIGN: A literature review of the basic biochemistry of the beta-oxidation pathway and clinical cases of defects of fatty acid metabolism are presented, and the diagnosis and treatment of such defects are discussed. MATERIAL AND METHODS: In many cases, a correct diagnosis will be made only if these disorders are specifically considered and appropriate tests are obtained, because results of screening tests for other organic acidemias are often normal in these entities. RESULTS: The first disorder of fatty acid metabolism was described only 20 years ago. Since then, at least 15 different inborn errors of metabolism that affect beta-oxidation have been identified, most in the past 10 years. Within the past 5 years, investigators have realized that a deficiency of one of these enzymes, medium-chain acyl coenzyme A dehydrogenase, may be one of the most common inborn errors of metabolism. This disorder may have a frequency equal to that of phenylketonuria in some populations in the United States and northern Europe. Approximately 1 to 3% of all unexplained deaths during infancy and childhood are probably related to disorders of beta-oxidation. Diagnosis of these disorders can be difficult because of the intermittent nature of the excretion of characteristic compounds. The mainstay of therapy for defects of beta-oxidation is avoidance of fasting. CONCLUSION: All patients with a suspected defect of fatty acid metabolism should be assessed and monitored by a specialist trained in the care of such patients. Continued improvements in the ability to diagnose and treat these disorders will be directly linked to new advances in the basic research on these enzymes. Movements to screen newborns for medium-chain acyl coenzyme A dehydrogenase are under way in some medical centers. Proposed tests include metabolite analysis or direct mutation analysis (or both) from blood spots from newborn screening cards already obtained for every newborn in the United States.