A Decade of Newborn Screening for Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD): Benefits, Complications and the Need for Long-Term Follow-Up

Background: Most infants with very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD) identified by newborn screening (NBS) are asymptomatic at the time of diagnosis and remain asymptomatic. It is not clear if this outcome is due to prompt diagnosis and initiation of therapy, or because of identification of individuals with biochemical abnormalities who will never develop symptoms. Methods: A 10 year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS . Main outcome measures were VLCAD activity in lymphocytes and cultured skin fibroblasts; overall capacity of long-chain fatty acid oxidation (LC-FAO flux) in cultured skin fibroblasts, ACADVL gene analysis and clinical outcome parameters. Findings: The median VLCAD activity in lymphocytes of the 64 patients, 27 diagnosed pre-NBS and 37 by NBS was respectively 5·4% (95% CI 4·0-8·3%) and 12·6% (95% CI 10·7-17·7%; p 10% 7 out of 12 diagnosed pre-NBS versus none by NBS experienced hypoglycemic events. Interpretations: NBS has a clear beneficial effect on the prevention of hypoglycemic events in patients with some residual enzyme activity, but does not prevent hypoglycemia nor cardiac complications in patients with very low residual enzyme activity. The effect of NBS on prevalence and prevention of myopathy-related complications remains unclear. This study illustrates the need for long-term follow-up studies of patients identified by NBS and comparison with patients identified before NBS to determine the true effects of NBS. Funding: ZonMW and Metakids Declaration of Interest: All authors declare that they have no competing interests. Ethical Approval: The study was approved by the medical ethics committee of the UMCU (METC 10–430/C; METC15-582/C). Informed consent was obtained for all patients participating in this study.