A patient with a urea cycle disorder (UCD) may develop hyperammonemic encephalopathy after starting valproic acid therapy. Prior to initiating valproic acid therapy a patient should be screened for clinical evidence of a possible urea cycle disorder.


While some patients with UCD are diagnosed as neonates, others may be diagnosed as infants, children or even adults (late onset disease).



(1) history of unexplained encephalopathy or coma

(2) history of encephalopathy associated with a protein load

(3) history of pregnancy-related or postpartum encephalopathy

(4) history of Reye's syndrome

(5) family history of urea cycle disorder

(6) family history of unexplained infant death

(7) history of protein avoidance


Signs and symptoms with neonatal onset:

(1) hypothermia

(2) lethargy

(3) vomiting

(4) failure to feed

(5) coma


Signs and symptoms:

(1) seizures

(2) apnea

(3) cyclic somnolence and lethargy

(4) unexplained mental retardation

(5) cyclic vomiting

(6) episodic extreme irritability or agitation

(7) unexplained amblyopia

(8) developmental delay

(9) ataxia


Laboratory findings:

(1) elevated plasma ammonia or glutamate

(2) low serum BUN (blood urea nitrogen)


A patient with findings suggestive of a urea cycle disorder should not receive valproate for seizure control.


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