A deficiency of argininosuccinate synthetase (ASD) can be suspected in a neonate with elevated serum ammonia. To discriminate the fact that the hyperammonemia is indeed due to ASD and not due to a deficiency in other urea cycle enzymes, one can assay for the serum concentration of citrulline and orotic acid. Which of the following would best describe the expected findings?

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In argininosuccinate synthetase deficiency, citrulline accumulates because it cannot be converted to argininosuccinate, leading to elevated citrulline levels. Orotate levels remain near normal because the block is after carbamoyl phosphate, which is the precursor for orotate. A urea cycle disorder (UCD) is likely in a neonate that has elevated serum ammonia appearing, not before, but between 24 and 48 hours after a normal term delivery. There are 3 hallmark symptoms associated with UCD. These are hyperammonemia, encephalopathy, and respiratory alkalosis. Thus, elevated serum ammonia is not, in and of itself, indicative of a specific defect in the urea cycle. An analysis of the levels of various amino and organic acids in the plasma and urine is the primary key to determining which defect led to the elevation in serum ammonia. Differential diagnosis of neonatal hyperammonemia as a consequence of a UCD can be accomplished by measurement of plasma citrulline and urinary orotic acid levels. Shown in Figure 29-9 is 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 citrulline demonstrates that it is >1000 _mM, it is confirmed that the clinical symptoms are due to a deficiency in argininosuccinate synthetase. In this circumstance, it is not necessary to assay for levels of urinary orotic acid, but they would be expected to be normal.

A Deficiency of Argininosuccinate Synthetase (ASD) Can Be Suspected in a Neonate