Newborn Screening for Metabolic Disorders: How Are We Doing, and Where Are We Going?

Owing to technological advances during the last decade, there has been a paradigm shift in the way that we diagnose patients with inherited metabolic disease. The introduction of tandem mass spectrometry (MS/MS),7 a technology with sufficient analytical sensitivity to measure metabolic biomarkers in small blood spot samples, has allowed us to shift from what was initially a diagnosis made after or during acute metabolic decompensation into an era in which diagnosis is made immediately in the newborn period. In this environment, the diagnosis of certain metabolic diseases frequently precedes the onset of symptoms, giving physicians an opportunity to prevent many of the catastrophic events that used to occur. To this point, disorders such as medium-chain acyl-CoA dehydrogenase (MCAD) deficiency now rarely initially present as the acute-onset liver failure that was previously seen in unscreened and consequently undiagnosed patients. Clinical outcomes for MCAD deficiency are now excellent, and data on some of the other screened disorders are starting to show the benefit of early diagnosis. Diagnostic technology continues to increase in its capability to provide early diagnosis of increasing numbers of these metabolic diseases as more biomarkers become identified. In this Q&A, 5 leading thinkers in the field provide their insights into where we presently stand in this area and where we might be headed in the future. Has there been a positive impact on patient care as a result of early diagnosis and implementation of the American College of Medical Genetics (ACMG) recommended-screening disorders? Piero Rinaldo: The implementation of the ACMG uniform panel has had a positive impact at multiple levels. The consistency of the panel has virtually eliminated the discrepancies between neighboring states, often a cause of heartbreaking events where parents have experienced significant morbidity and mortality of their child that would not have happened if their child …