Case Study

A Metabolic Emergency

by George T. Mandy, MD

Case presentation

This 3360-gram Hispanic male was born in Harlingen, Texas to a 19-year-old mother at 41 weeks’ gestation by spontaneous vaginal delivery after an uncomplicated pregnancy. The Apgar scores were 9/9 at 1 and 5 minutes of life. The baby was admitted to the normal newborn nursery where poor feeding was noted, although the baby did complete 2 one-ounce feedings before discharge at 24 hours of life. Also noted, when the hepatitis vaccination was given, he did not cry. The mother noted on the second day of life that the baby had continued poor feeding, increasing somnolence, and jaundice, and she took the baby to a local hospital. The emergency room did a sepsis evaluation, and the baby was admitted to the NICU where a serum ammonia level was ordered. The ammonia was 629 μmol/L (normal 55 μmol/L).

Arrangements were made to transfer the patient by air transport to Houston. When the neonatal team of the Texas Children’s Hospital Kangaroo Crew® Intensive Care Transport Service arrived in Harlingen, the baby was hypotensive and apneic with rhythmic movements of the extremities. He was intubated, given phenobarbital and two 10 mL/kg 5% albumin bolus infusions, and was started on a continuous arginine infusion.

On admission to Texas Children’s Hospital, several services became involved: neonatology, pediatric surgery, renal, and genetics. The baby’s physical exam showed a minimally jaundiced, severely neurologically depressed term infant. The ammonia level was 1431 μmol/L. Hemodialysis was started; 4 hours later, the ammonia level was 119 μmol/L and dialysis was stopped.

A few hours after admission, a diagnosis of carbamyl phosphate synthetase deficiency was made, based on elevated alanine and glutamine levels and an absence of citrulline in the serum amino acid panel coupled with an elevated urine orotic acid level.

After dialysis, the baby received an infusion of glucose with insulin to suppress catabolism and the accompanying protein breakdown so as to minimize ammonia accumulation. The infant also received a continuous infusion of arginine, phenylacetate, and sodium benzoate. Despite these measures, the serum ammonia rebounded to 524 μmol/L 24 hours later and the baby required another course of hemodialysis. On the 3rd hospital day, specific amino acid support was started. On the 4th hospital day, the baby underwent open liver biopsy to confirm the initial diagnosis. At that time, a G-tube was inserted to optimize administration of medication and nutritional support. Head ultrasound, EEG studies, and neurological exam were normal at discharge on day of life 29 to await liver transplantation. The infant’s discharge weight was 4115 grams.

Denouement

Infants with urea cycle disorders must be treated with urgency as soon as the diagnosis is suspected in order to prevent permanent neurological injury. Any newborn term infant presenting with lethargy and hypotonia with or without respiratory symptoms must have serum ammonia and lactic acid levels measured as part of the initial evaluation. Once an elevated level of either is found, genetic consultation should be sought and referral made to a pediatric center with appropriate resources (ie, pediatric surgery, renal, neonatology, genetics, and pharmacologic expertise). These specialists are necessary to promptly establish vascular access, institute hemodialysis, and initiate further pharmacologic support. This approach also means that treatment should be initiated prior to transport and en route. The prompt institution of these measures will contribute to the best possible outcome.