Lethal Undiagnosed Very Long-Chain Acyl-CoA Dehydrogenase Deficiency with Mild C14-Acylcarnitine Abnormalities on Newborn Screening

Newborn screening identifies patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency with disease-specific acylcarnitine profiles. We here present a patient who died at 16 months during a gastrointestinal infection because of undiagnosed VLCADD. The primary acylcarnitine profile on newborn screening performed at 55 h of life revealed C14-acylcarnitine values and ratios within the 1st percentile VLCAD disease range and C12-acylcarnitine values and ratios within the 10th percentile disease range. The acylcarnitine cumulative percentiles in neonatal dried blood spots analyzed by tandem mass spectrometry have been obtained by participants of the Region 4 Stork collaborative project. A secondary screen was requested by the screening laboratory as a result of the initial screen and was normal on day 8 of life. With the initial acylcarnitines only within the 1st–10th percentile disease range, newborn screening for VLCAD deficiency was in the end considered normal. The most important lesson learned is that acylcarnitine profiles from healthy newborns during catabolism and VLCAD-deficient patients can in certain cases not be distinguished by any means. With a known high incidence of false positive cases for VLCADD on newborn screening, it finally remains unknown, whether forced anabolism in the first days of life may result in normal acylcarnitine profiles in VLCAD-deficient patients resulting in missed cases and false negatives on newborn screening. Our observations are of great significance since they demonstrate the limitations of acylcarnitine analysis as screening tool for VLCAD-deficiency.