Carbamoyl phosphate synthetase I deficiency

What else is it called?

  • CPS
  • CPS I Deficiency

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What causes it?

Carbamoyl phosphate synthetase I deficiency belongs to a group of disorders called the Urea Cycle Disorders (UCDs). These are inborn errors of metabolism caused by a deficiency of one of the enzymes in the urea cycle that is responsible for the removal of ammonia. When the body digests protein, it is broken down into small molecules known as amino acids. These travel through the blood stream and are transported to the cells. Most of us eat more protein than we need, and the excess amino acids are converted into a toxic substance known as ammonia. In the liver, the ammonia is converted to urea, which is harmless, and excreted in the urine. In Urea Cycle Disorders one of the enzymes does not function properly and ammonia is not removed from the blood stream. This causes a build-up of ammonia in the body with high blood ammonia concentrations (hyperammonaemia) and causes the symptoms. In this disorder defects in the CPS1 gene cause a deficiency of the enzyme carbamoyl phosphate synthetase I.

How common is it?

We do not know the exact prevalence of this disorder. It is estimated to affect between 1 in 150,000 to 1 in 200,00 live births.

What are the signs and symptoms?

Symptoms generally occur within the first few days of life in the form of a hyperammonaemic crisis. These occur when ammonia builds up. Signs and symptoms of a crisis may include:

  • Poor feeding
  • Vomiting
  • Floppiness
  • Excessive sleepiness
  • Rapid breathing
  • Dehydration (lack of body fluids)
  • Seizures

The effects of high ammonia can quickly become life-threatening if untreated.

Crises can be triggered at any time of life by eating high protein foods, fasting (long periods without eating), and illness and infection. Signs of high ammonia include

  • Confusion
  • Irritability
  • Headache
  • Lethargy
  • Weakness
  • Cognitive problem

There may be learning difficulties and delays to normal development, like walking and talking.

In some people with carbamoyl phosphate synthetase I deficiency, signs and symptoms may be less severe and appear later in life.

How is it diagnosed?

The diagnosis is suspected in a patient with high ammonia levels because of the pattern of chemicals in the blood and urine. The diagnosis is confirmed by finding the mutation in the CPS I gene.

Can it be treated?

This disorder can be managed with a low protein diet, citrulline and arginine supplements as required, and nitrogen scavenger therapy (sodium benzoate and/or sodium or glycerol phenylbutyrate). A specialist dietitian will help you to manage your diet and ensure that you have a balanced diet adapted to your changing needs. Tube feeding may be necessary to give regular feeds. This will ensure that energy, nutrient and fluid needs are met.

Treatment includes avoiding known triggers. Your consultant will give you an emergency regimen to follow if you feel unwell which will reduce the breakdown of protein and the build-up of ammonia. It is important that treatment is started immediately and as prescribed. If symptoms persist or you are worried you should go immediately to hospital and update your metabolic team.

Do my family need to be tested?

CPS I Deficiency is inherited from the genes of the parents by a method called autosomal recessive inheritance. This is when a child inherits a gene for the disease from both parents. If a child receives one normal gene and one gene with the disease, the child will be a carrier for the disease and usually does not show any symptoms. The risk of passing on CPS I Deficiency to a child from a couple who are both carriers is 25%, there is a 50% chance that their child will be a carrier and there is a 25% chance that the child would not have the condition nor be a carrier. This risk is the same for each pregnancy.


Relevant Organisations


All information accurately referenced by Metabolic Support UK, however, should you require access to our references, please contact us by email:

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