Long-Term Outcomes of Adolescents and Young Adults Identified by Metabolic Newborn Screening

Abstract

Objective: Although newborn screening (NBS) programs were expanded with the implementation of tandem mass spectrometry in the late 1990s, the impact on long-term clinical and cognitive outcomes of adolescents and young adults with inherited metabolic diseases (IMDs) has remained fairly unknown for most IMDs.

Methods: A prospective, multicenter, observational study is performed in Southwest Germany (NGS2025, DRKS-ID: DRKS00013329). For systematic follow-up from preschool up to adulthood, individuals with IMDs identified by NBS between 1999 and 2014 were included.

Results: In total, 257 (124 boys, 133 girls) screened individuals with at least 1 study visit in adolescence were followed until median age of 13.7 years. During the observation period, most did not develop permanent disease-specific signs (70.1%) or metabolic decompensations (55.2% of those at risk), had normal cognitive outcome (81.4%; IQ mean [SD], 98 [15]), and attended regular primary (91.2%) and secondary schools (90.8%). Nonetheless, NBS and early start of treatment did not prevent metabolic decompensations in 69 (44.8%) individuals at risk, and in 33 of them, metabolic decompensation occurred already before the NBS result was available. Permanent disease-specific symptoms were more frequently observed in patients experiencing metabolic decompensations compared with those without decompensations (75% vs 12.8%). Reliable therapy adherence was associated with better long-term outcome.

Conclusion: NBS for IMDs is a highly successful program of secondary prevention for most early-diagnosed and early-treated individuals with an IMD, allowing the start in an independent life; however, therapeutic effectiveness and quality remain a relevant limitation in some diseases.