A 2-day-old male newborn develops lethargy, poor feeding, vomiting, and rapid respirations. He was delivered at term after an uncomplicated pregnancy. His brother died in infancy. He has been breast-fed since birth. Serum studies indicate an increased ammonia concentration and a nondetectable citrulline concentration. Urine orotic acid concentration is markedly increased. A deficiency in which of the following enzyme activities is the most likely cause of these findings?

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The symptoms and lab findings suggest a urea cycle disorder, specifically ornithine transcarbamylase deficiency, which is characterized by hyperammonemia, low citrulline, and elevated orotic acid in urine. Differential diagnosis of neonatal hyperammonemia, as a consequence of a UCD can be accomplished by measurement of plasma citrulline and urinary orotic acid levels. Refer to Figure 29-9 which shows the standard differential diagnosis chart for determining which of the 4 possible neonatal UCDs are the causes of the hyperammonemia. First, the hyperammonemia appears in the absence of any significant acidosis or ketosis. If analysis of serum cuitrulline demonstrates undetectable levels, then deficiencies in argininosuccinate lyase and argininosuccinate synthetase can be eliminated as causes of the symptoms. Assay for levels of urinary orotic acid will allow a discrimination between carbamoyl phosphate synthetase I and ornithine transcarbamoylase deficiencies. Since the levels of orotic acid were found to be elevated, the symptoms must be due to deficiency in ornithine transcarbamoylase (OTC).

A 2-Day-Old Male Newborn Develops Lethargy, Poor Feeding, Vomiting, and Rapid