Urea cycle disorders (UCDs) are inherited defects of ammonia detoxification. Hyperammonaemia can cause cerebral oedema, encephalopathy, seizures, coma and permanent brain injury.
In UCDs, seizure treatment alone is not enough: the ammonia crisis itself must be treated urgently.
The urea cycle
The urea cycle converts toxic nitrogen waste into urea for excretion.
Disorders involve enzymes or transporters including NAGS, CPS1, OTC, ASS1, ASL, ARG1, SLC25A15 and others.
Neonatal presentation
Severely affected newborns can appear normal for the first day or two, then develop poor feeding, vomiting, lethargy, abnormal breathing, seizures, posturing and coma.
Hyperammonaemia is the emergency
Ammonia is directly neurotoxic and can cause rapid cerebral swelling.
Any unexplained encephalopathy with seizures should prompt urgent ammonia measurement.
Subclinical seizures
Seizures during severe hyperammonaemia may be electrographic without obvious convulsive movement.
Continuous EEG can therefore be useful in critically ill neonates.
Later-onset disease
Partial defects can present in childhood or adulthood with recurrent vomiting, confusion, behavioural change, headaches, ataxia, seizures or episodic coma.
Episodes may be triggered by infection, fasting, surgery, postpartum catabolism or high protein load.
OTC deficiency
Ornithine transcarbamylase deficiency is X-linked and is the most common UCD.
Females can be symptomatic because of X-chromosome inactivation and may present for the first time in adulthood.
Diagnosis
Urgent tests include plasma ammonia, plasma amino acids, blood gas and urine orotic acid, interpreted together.
Molecular testing confirms the specific disorder.
Acute treatment
Treatment aims to stop catabolism, reduce ammonia production and remove excess nitrogen.
High-calorie intravenous support, nitrogen-scavenging medicines and disorder-specific therapy are used in specialist protocols.
Dialysis
Severe hyperammonaemia may require haemodialysis or haemofiltration because ammonia can rise faster than medicines can remove it.
N-carbamylglutamate
N-carbamylglutamate is targeted therapy for NAGS deficiency and can restore urea-cycle activity.
It is also used in selected secondary hyperammonaemic states under specialist guidance.
Seizure treatment
Antiseizure medicines may be required during acute crises, but seizure control does not mean the hyperammonaemia has resolved.
The metabolic emergency must be corrected simultaneously.
Long-term management
Many people require protein management, essential amino-acid supplementation, nitrogen-scavenging treatment and emergency illness plans.
Liver transplantation can be considered in selected severe UCDs.
Neurological outcome
Outcome is strongly related to the severity and duration of hyperammonaemia.
Repeated crises can cause cumulative cognitive and motor impairment.
Worldwide access
Plasma ammonia is a simple but time-critical test. Delays in obtaining or correctly handling the sample can cost valuable time.
Access to dialysis, specialist metabolic medicines and transplantation varies globally.
The central point
In a urea-cycle crisis, seizures are a sign of ammonia toxicity. Treating the seizure without rapidly lowering ammonia leaves the underlying brain injury process active.
Related reading
Sources
Medical note: suspected hyperammonaemia is a medical emergency requiring urgent specialist treatment.
Evidence checked: September 2026.