[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Ornithine transcarbamylase (OTC) deficiency

[Conditions](https://durgical.com/en/conditions/) · [Metabolism: amino acids and the urea cycle](https://durgical.com/en/conditions/)

# 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

Tap one to see what it is and open it in 3D.

- [Liver](https://durgical.com/en/anatomy/liver/)
- [White matter](https://durgical.com/en/anatomy/white-matter-of-telencephalon/)
- [Frontal lobe](https://durgical.com/en/anatomy/superior-frontal-gyrus/)
- [Thalamus](https://durgical.com/en/anatomy/thalamus/)

## In biochemistry

- [Urea cycle: Step 1 · Ornithine transcarbamylase (OTC)](https://durgical.com/en/biochemistry/pathways/urea-cycle/#paso-1)
- [Ammonia (ammonium)](https://durgical.com/en/biochemistry/molecules/ammonia/)
- [Glutamine](https://durgical.com/en/biochemistry/molecules/glutamine/)
- [Ornithine transcarbamylase (OTC)](https://durgical.com/en/biochemistry/enzymes/ornithine-transcarbamylase/)
- [Urea and blood urea nitrogen (BUN) as lab tests](https://durgical.com/en/biochemistry/topics/urea-and-blood-urea-nitrogen-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

## Red flags

- Lethargy or coma in a newborn without clear infection
- Encephalopathy after childbirth
- Very high ammonia

## 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](https://durgical.com/en/anatomy/white-matter-of-telencephalon/).

## 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](https://durgical.com/en/anatomy/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

Think of the answer, then tap the question to see it.

## 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.

[Add to my cards (4)](https://durgical.app/estudiar/?add=/en/conditions/ornithine-transcarbamylase-deficiency/)

## Related conditions

- [Hyperammonaemia](https://durgical.com/en/conditions/hyperammonaemia/)
- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Portal hypertension](https://durgical.com/en/conditions/portal-hypertension/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Ornithine transcarbamylase deficiency: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/ornithine-transcarbamylase-deficiency/) (MedlinePlus, US National Library of Medicine, 2026); [OTC gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/otc/) (MedlinePlus, US National Library of Medicine, 2026); [Hereditary urea cycle abnormality: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000372.htm) (MedlinePlus, US National Library of Medicine, 2026).

[← All conditions](https://durgical.com/en/conditions/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/conditions/ornithine-transcarbamylase-deficiency/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/ornithine-transcarbamylase-deficiency/