Conditions · Metabolism: amino acids and the urea cycle
Ornithine transcarbamylase (OTC) deficiency !
The most common urea cycle disorder: the liver cannot clear ammonia well, so it builds up and damages the brain.
Updated 2026-11-01
Structures involved
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In biochemistry
- Urea cycle: Step 1 · Ornithine transcarbamylase (OTC)
- Ammonia (ammonium)
- Glutamine
- Ornithine transcarbamylase (OTC)
- Urea and blood urea nitrogen (BUN) as lab tests
What it is
An X-linked inherited disease from lack of ornithine transcarbamylase, the second enzyme of the urea cycle.
Who gets it
Estimates range from 1 in 14,000 to 1 in 77,000 people; late-onset forms are probably underdiagnosed.
Causes
- Variants of the OTC gene on the X chromosome; many are new
Risk factors
- Male sex (severe forms)
- Carrier mother
- Triggers: infection, fasting, childbirth, very high-protein diet, valproate or corticosteroids
Pathophysiology
Without OTC, carbamoyl phosphate cannot join ornithine: ammonia and glutamine build up and citrulline falls. Spare carbamoyl phosphate spills into the cytosol and forms orotic acid. In the brain, ammonia becomes glutamine inside astrocytes, which swell: cerebral oedema.
Classification
- Neonatal in males: coma in the first days
- Late-onset in males or carrier females: triggered crises, protein aversion
Symptoms and signs
- A newborn who refuses feeds, vomits and becomes drowsy
- Hyperventilation (respiratory alkalosis)
- Seizures and coma
- In late forms: cyclic vomiting, headache, confusion and meat avoidance
Diagnosis
- Clinical
- Encephalopathy with respiratory alkalosis and high ammonia; affected males on the maternal side.
- Tests
- Very high plasma ammonia; high glutamine and low citrulline in plasma amino acids; high urinary orotic acid; OTC gene testing.
- Imaging
- Brain MRI in crises: oedema and lesions of cortex and white matter.
Treatment
- Acute
- In a crisis: stop protein, give glucose and lipids to halt catabolism, nitrogen scavengers (sodium benzoate and phenylacetate), arginine and haemodialysis if ammonia is very high
- Lifestyle
- Low-protein diet with essential amino acids
- Medical
- Oral phenylbutyrate or glycerol phenylbutyrate and citrulline
- Surgical
- Liver transplant in severe forms
Complications
- Cerebral oedema and death in a crisis
- Intellectual disability
- Epilepsy
Prognosis
Neonatal forms have high mortality and sequelae; well-treated late forms can allow a near-normal life.
Prevention
- Genetic counselling and carrier testing
- Emergency plan for infections or surgery
Test yourself
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How is OTC deficiency inherited?
X-linked; males have the severe forms and some carrier females have crises.
Which lab pattern marks it?
High ammonia, low citrulline, high glutamine and high urinary orotic acid.
Why do scavengers such as phenylbutyrate lower ammonia?
They bind glutamine or glycine and are excreted in urine, taking nitrogen out without the urea cycle.
Which acid–base disorder is typical at onset?
Respiratory alkalosis, because ammonia stimulates the respiratory centre.
Related conditions
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Ornithine transcarbamylase deficiency: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); OTC gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Hereditary urea cycle abnormality: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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