Introduction

Inborn errors of metabolism that present in the neonatal period can have clinical, biochemical, and neuroradiologic features similar to those of hypoxic–ischemic encephalopathy (HIE). Both metabolic disorders and HIE are associated with severe neurologic distress, metabolic acidosis, and multiorgan system involvement. In general, the patterns of brain injury are different when HIE and inborn errors of metabolism are compared. However, some metabolic disorders may have neuroradiologic findings similar to those seen in HIE. Although inborn errors are rare individually, as a group they affect approximately 1 in 1000 neonates. It is crucial to consider these disorders in the differential diagnosis of patients who present with nonspecific features suggestive of sepsis or asphyxia. Prompt diagnosis may not only prevent mortality or significant morbidity, but also allows the clinician to provide the family with accurate genetic counseling. In this chapter, patterns of brain injury and systemic complications that occur in HIE and metabolic disorders are reviewed. Specific inborn errors of metabolism with clinical presentations that may be seen in patients with HIE are discussed further. For a more comprehensive review of inborn errors of metabolism, the reader is referred to standard metabolic texts.

Patterns of brain injury in HIE and inborn errors of metabolism

Neonatal hypoxic–ischemic brain injury may be caused by localized infarction or a diffuse ischemic insult. Focal ischemic infarction in the neonate typically presents with lethargy, hypotonia, or seizures. Metabolic causes of focal ischemia are listed in Table 19.1, but will not be reviewed in this chapter.