A 2-day-old infant boy delivered by normal labor (with no known prenatal risk factors) has become lethargic and requires stimulation for feeding. When vomiting and hyperventilation ensued, routine laboratory results showed blood urea nitrogen (BUN) less than 1 mg/dL. The infant quickly lapses into a coma and was placed on a ventilator. Bulging of the fontanel suggested an intracranial hemorrhage, but a CT scan revealed only cerebral edema. Within several hours, the infant dies. Death is ascribed to sepsis; however, a postmortem analysis of the plasma samples taken at admission showed dramatically elevated serum ammonia and citrulline levels 100 times normal. Which of the following represents the enzyme deficiency associated with these severe neonatal symptoms?

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Quizplus · Accepted Answer

The symptoms and elevated serum ammonia and citrulline levels suggest a urea cycle disorder, specifically a deficiency in argininosuccinate synthetase, which leads to citrullinemia. The clinical presentation of patients with defects in several enzymes of urea synthesis is virtually identical. These enzymes are CPS-I, ornithine transcarbamoylase (OTC), argininosuccinate synthetase (AS), and argininosuccinase. The hallmark of these urea cycle enzyme defects is a normal birth with no known prenatal risk factors. Within 24-72 hours after birth the infant becomes lethargic and requires stimulation for feeding. Additional symptoms develop within hours, including vomiting, increased lethargy, hypothermia, and hyperventilation. The hyperventilation is often misdiagnosed as pulmonary disease. Sepsis is often suspected. Routine blood work indicates a reduced BUN. Lack of proper intervention will lead to coma and death. Correct analysis of hyperammonemia is paramount to proper treatment as this is indicative of a urea cycle defect when presenting in the newborn. Analysis of plasma amino acids can aid in the differentiation of which enzyme is defective. Elevated citrulline (to 100 times normal levels) results from a deficiency in AS.

A 2-Day-Old Infant Boy Delivered by Normal Labor (With No