Inborn Errors of Metabolism and Other Genetic Disorders with Features of Neonatal Encephalopathy

Inborn errors of metabolism and abnormalities in many single genes related to neuronal function can have clinical, biochemical, and neuroradiologic features similar to those of neonatal encephalopathy caused by environmental factors, such as in-utero hypoxia, ischemia, inflammation, or infection. Both genetic disorders and neonatal encephalopathy secondary to environmental factors, such as hypoxic–ischemic encephalopathy (HIE) or fetal inflammatory response syndrome, may be associated with severe neurologic distress, metabolic acidosis, brain imaging abnormalities, and multiorgan system involvement. Although newborn screening using tandem mass spectrometry (MS/MS) can detect numerous metabolic disorders, many inborn errors of metabolism that present with HIE-like features will be missed, so specialized biochemical tests or next-generation gene sequencing studies are required in order to establish a diagnosis. Prompt diagnosis of an underlying genetic disorder not only may prevent mortality or significant morbidity but also may allow the clinician to provide the family with comprehensive genetic counseling.