P1.026: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Manifesting in a Neonate Following Cardiac Arrest

Introduction: Medium-chain Acyl-coenzyme A Dehydrogenase Deficiency (MCADD) is an atypical etiology of cardiorespiratory arrest in the pediatric population. It is a rare autosomal recessive inborn error of metabolism (prevalence is 1/50,000 births). MCADD is caused by a decreased level of medium chain acyl-coenzyme A dehydrogenase enzyme, which breaks down fatty acids for energy. Individuals with MCADD appear phenotypically normal at birth with onset of presentation between 12 months and 3 years of age. The disorder may be asymptomatic; it is commonly characterized by hypoketotic hypoglycemia, seizures, and lethargy. In most severe cases, undiagnosed MCADD can lead to cardiac arrest and death, so early recognition is key to treatment response and overall prognosis.

Case Description: We present a case of a 2-day old Caucasian male with no contributory past medical or exposure history presenting in cardiorespiratory arrest with fixed and dilated pupils. Initial concern was for early onset sepsis versus a primary cardiac etiology. However, serial bedside echocardiograms were unrevealing for any anatomic/congenital abnormalities. Initial blood, urine and cerebrospinal fluid cultures returned negative for infection, and concern was raised for an inborn error of metabolism. Brain MRI showed diffusion restriction in the basal ganglia region suggestive of hypoxic ischemic encephalopathy. Newborn screen returned at 12 days of life and confirmed MCADD: C8:17.7, C10:1.43, C8/C10: 12.37. Hypoglycemia panel genetic testing (tests for 120 genes associated with recurrent hypoglycemia) returned positive, Gene: acyl-Coenzyme A dehydrogenase (ACADM) variant: c.985A>G (p-Lys329Glu), zygosity: homozygous. Per Genetics’ recommendations, the patient was managed with levocarnitine (L-Carnitine) and riboflavin supplementation.

Discussion: L-Carnitine, an amino acid derivative, may be depleted in MCADD as it remains conjugated to the accumulated medium chain fatty acids and is excreted as acylcarnitine. Supplementation of L-Carnitine helps shuttle fatty acids across the mitochondrial membrane to make energy and prevent metabolic crisis in MCADD. Riboflavin is also a vital component of mitochondrial energy production and helps generate adenosine triphosphate (ATP), which is needed for fatty acid oxidation. This case highlights that MCADD can mimic sepsis in neonates and is difficult to identify, especially within the first few days of life.

Conclusion: Neonates with undiagnosed MCADD are at risk of metabolic crisis, cardiopulmonary arrest, and death. MCADD should be considered in term infants with severe hypoglycemia who are exclusively breastfed without other risk factors such as positive/unknown Group B Streptococcus status, infant of a diabetic mother and lack of prenatal care. It also prompts the consideration of more frequent glucose monitoring in exclusively breastfed infants with feeding difficulties in the nursery.