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.