Laboratory Studies

Routine laboratory studies are of no diagnostic help. The clue to the presence of carbamoyl phosphate synthetase (CPS) deficiency may be a BUN level below the reference range. In contrast to older studies, this is merely a clue, is not always present, may occur in early fasting, and is quite unreliable. Nonetheless, when present, a BUN level below the reference range should trigger a search for hyperammonemia.

Liver function is normal unless hypoxia has occurred in association with seizures. The same is true of renal function.

The sole laboratory criterion for early diagnosis is a blood ammonia level. Obtain a blood level simultaneously with the usual laboratory workup as a part of the investigation of a critically ill neonate or infant. Determine blood ammonia level in adults with unexplained lethargy or coma.

Ammonia levels are usually 10-20 times higher than reference range.

Ammonia values greater than 1000 mg/dL are common. Blood amino acid changes are not specific to provide a diagnosis but are important in the differentiation of CPS deficiency from other urea cycle disorders.

Urine orotic acid levels are within the reference range.

Urine organic acid analysis is important to rule out organic acid disorders.

Definitive testing no longer requires liver biopsy; molecular diagnosis is available.

Postmortem findings are completely nonspecific, and, as a mitochondrial enzyme, CPS I is liable to rapid inactivation. Therefore, obtain hepatic samples for enzyme diagnosis during life, if possible, or immediately after death.

Imaging Studies

A report suggests that single-voxel magnetic resonance spectroscopy permits the monitoring of brain glutamine and brain glutamate levels. This may be a more accurate means of monitoring the effects of an acute hyperammonemic episode on the brain than monitoring blood ammonia levels as treatment proceeds.

A 2013 report details the MRI findings in neonates.^[6]

Other Tests

Electroencephalography reveals nonspecific diffuse encephalopathy.

Molecular genetic diagnosis is available.^[7]

Procedures

Approach lumbar puncture with great caution because of the potential for cerebral edema.

Treatment & Management

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Media Gallery

Compounds comprising the urea cycle are numbered sequentially, beginning with carbamyl phosphate (1). At this step, the first waste nitrogen is incorporated into the cycle; at this step, N-acetylglutamate exerts its regulatory control on the mediating enzyme, carbamyl phosphate synthetase (CPS). Compound 2 is citrulline, the product of condensation between carbamyl phosphate (1) and ornithine (8); the mediating enzyme is ornithine transcarbamylase. Compound 3 is aspartic acid, which is combined with citrulline to form argininosuccinic acid (ASA) (4); the reaction is mediated by ASA synthetase. Compound 5 is fumaric acid generated in the reaction that converts ASA to arginine (6), which is mediated by ASA lyase.

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