Sudden neonatal death in individuals with medium-chain acyl-coenzyme A dehydrogenase deficiency: limit of newborn screening

Abstract

Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency is the most common disorder of mitochondrial β-oxidation of fatty acids resulting in hypoketotic hypoglycemia, hepatopathy, and often fatal outcome in undiagnosed children. Introduction of tandem mass spectrometry–based newborn screening programs in the late 1990s has significantly reduced morbidity and mortality in MCAD deficiency; however, neonatal death in individuals with early disease manifestation and severe hypoglycemia may still occur. We describe the fatal disease course in eight newborns with MCAD deficiency, aiming to raise awareness for early clinical symptoms and the life-saving treatment, and promote systematic post-mortem protocols for biochemical and genetic testing, necessary for correct diagnosis and counselling of the family if unexpected death occurred in the neonatal period.Conclusion: Early newborn screening and awareness for clinical symptoms is lifesaving in MCAD deficiency, which may present with fatal neonatal crisis. Systematic post-mortem diagnostic protocols are needed for sudden neonatal deaths.What is Known:• Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency identified by newborn screening has an excellent outcome.• Fatal neonatal crises occur in the first days prior to screening.What is New:• Poor feeding, no monitoring of blood glucose, and homozygosity of the common gene variant (c.985A > G) are major risk factors for fatal neonatal crisis in MCAD deficiency.• Post-mortem diagnostic protocols are indispensable for correct diagnosis and counselling of the family if unexpected death occurred in the neonatal period.