Impact of newborn screening on the reported incidence and clinical outcomes associated with medium- and long-chain fatty acid oxidation disorders

Fatty acid oxidation disorders (FAODs) are potentially fatal inherited disorders for which management focuses on early disease detection and dietary intervention to reduce the impact of metabolic crises and associated spectrum of clinical symptoms. They can be divided functionally into long-chain (LC-FAODs) and medium-chain disorders (almost exclusively deficiency of medium-chain acyl–coenzyme A dehydrogenase). Newborn screening (NBS) allows prompt identification and management. FAOD detection rates have increased following the addition of FAODs to NBS programs in the United States and many developed countries. NBS-identified neonates with FAODs may remain asymptomatic with dietary management. Evidence from numerous studies suggests that NBS-identified patients have improved outcomes compared with clinically diagnosed patients, including reduced rates of symptomatic manifestations, neurodevelopmental impairment, and death. The limitations of NBS include the potential for false-negative and false-positive results, and the need for confirmatory testing. Although NBS alone does not predict the consequences of disease, outcomes, or management needs, subsequent genetic analyses may have predictive value. Genotyping can provide valuable information on the nature and frequency of pathogenic variants involved with FAODs and their association with specific phenotypes. Long-term follow-up to fully understand the clinical spectrum of NBS-identified patients and the effect of different management strategies is needed.