A newborn that developed seizures 2 days after birth was diagnosed with elevated serum NH4+, glutamate, and alanine. A neonatal urea cycle defect was suspected so a urinalysis was performed to assay for orotic acid and serum assayed for citrulline. The levels of both were found not to be elevated. A defect in which enzyme of the urea cycle would most likely account for the symptoms observed in this infant?

Question

Quizplus · Accepted Answer

The absence of elevated orotic acid and citrulline levels suggests a defect in carbamoyl phosphate synthetase I (CPS-I), as this enzyme deficiency would lead to hyperammonemia without the accumulation of orotic acid or citrulline.  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 insignificant, the symptoms must be due to deficiency in carbamoyl phosphate synthetase I.

A Newborn That Developed Seizures 2 Days After Birth Was