Newborn screening for medium chain acyl-CoA dehydrogenase deficiency: evaluating the effects on outcome

Abstract

Although individually rare, inborn errors of metabolism represent a potentially preventable cause of death and disability. Tandem mass spectrometry allows a number of these disorders to be detected in a single step. Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most important of these disorders. However, public health decisions on whether or not to implement new screening programmes rely on evidence regarding benefits and harms. This article reviews existing published evidence for newborn screening for MCADD and highlights where further information is required for public health decision making. This review reveals that important uncertainties remain about performance and outcome, including criteria and thresholds for defining a positive screening result, diagnostic criteria, test performance and longer-term outcome. Notably, despite a combined experience of screening well over one million infants, there has been no report of a systematic follow-up of longer-term outcome in affected infants detected by screening. Prospective data on mortality, neurological outcome, and cognitive function are required to assess the effectiveness of screening. Additionally, the impact of screening and treatment on the families of infants with true, borderline, and false positive diagnoses needs to be taken into account.