Inborn Errors of Metabolism Masquerading as Hypoxic-Ischemic Encephalopathy

After completing this article, readers should be able to: 1. Compare the clinical features of hypoxic-ischemic encephalopathy and inborn errors of metabolism. 2. Review the metabolic disorders that may present with isolated neonatal seizures. 3. Review the metabolic disorders that may present with lactic acidosis, hypotonia, and systemic involvement. 4. Compare patterns of brain injury in hypoxic-ischemic encephalopathy and inborn errors of metabolism. Because inborn errors of metabolism can present in the neonatal period with neurologic distress, metabolic acidosis, and multiorgan system involvement, similar to features encountered in hypoxic-ischemic encephalopathy (HIE), an underlying metabolic disorder may go undiagnosed unless the clinician maintains a high index of suspicion and performs appropriate diagnostic testing. Although expanded newborn screening using tandem mass spectrometry (MS/MS) undoubtedly will detect many children who have metabolic disorders, this testing will not necessarily find neonates who have metabolic disorders that present with HIE-like features. In such cases, specialized testing of blood, urine, or cerebrospinal fluid (CSF) frequently is necessary to make the diagnosis and allow accurate genetic counseling. HIE typically occurs in term infants (gestation >37 wk) who display signs of distress before delivery, require resuscitation at birth, and develop neurologic abnormalities in the first 24 hours after delivery. (1) Perinatal asphyxia affects 3 to 5 infants per 1,000 live births, with encephalopathy occurring in 25% and death in an additional 30%. (2)(3) Although inborn errors of metabolism are rare individually, as a group they affect approximately 1 in 1,000 neonates, (4) mandating inclusion in the differential diagnosis of patients who present with nonspecific features suggestive of sepsis or asphyxia. Three criteria are essential to diagnose the presence of an acute intrapartum hypoxic event: 1) evidence of a metabolic acidosis in intrapartum fetal, umbilical arterial cord, or very early neonatal blood sample (pH <7.00 and base deficit ≥12 mmol/L); 2) …