The most common form of the disease presents in
the neonatal period with symptoms from hyperammonemia caused by protein
intake at 24 to 72 hours of age. Poor feeding and lethargy progress to
vomiting, irritability, impaired consciousness, tachypnea, seizures, and
apnea. Intracranial pressure is usually increased because of cerebral edema.
If unrecognized, the condition progresses to coma and finally death.
Surviving infants usually show a lower intelligence quotient. However, some
children present later with a subacute form of citrullinemia, which may
manifest as mental retardation and other neurologic symptoms such as ataxia.
They may show episodic vomiting and hyperammonemia triggered by minor
illnesses or other catabolic episodes. The late-onset form of the disease,
designated type II, occurs in late childhood or adulthood. Symptoms include
enuresis, delayed menarche, insomnia, recurrent vomiting, tremors, episodes
of confusion after meals, lethargy, hallucinations, behavioral changes,
seizures, and brief episodes of coma. Independent of the type of
citrullinemia, the majority of these patients die within a few years after
symptom onset. Treatment in the neonatal period includes supportive therapy,
intravenous glucose and insulin to suppress the protein catabolism, and use
of sodium benzoate and phenylacetate to provide an alternative pathway for
nitrogen excretion. Subsequent care depends upon restriction of protein
intake to the minimal amount necessary for growth, use of α-keto
analogues of essential amino acids, and arginine supplementation. Subsequent
episodes of hyperammonemia, triggered by inappropriate diet, drugs (e.g.,
valproic acid, haloperidol), or illness causing decreased caloric intake and
increased protein catabolism can be managed with intravenous glucose and
arginine. Orthotopic liver transplantation has been used successfully to
treat citrullinemia type II.