Citrullinaemia Type 1

What else is it called?

  • ASS Deficiency
  • Argininosuccinate Synthetase Deficiency
  • Citrullinuria
  • Inborn Error of Urea Synthesis, Citrullinaemia Type I
  • Urea Cycle Disorder, Citrullinaemia Type

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What causes it?

This belongs to a group known as the Urea Cycle Disorders. These conditions affect the way your body gets rid of ammonia.

Protein can be found in meat, eggs, milk, fish, cheese, and bread etc. When you eat protein, your body gets to work breaking it down into amino acids. These are used for different roles throughout the body. Any that is left over is broken down by enzymes into smaller substances, including ammonia. In large amounts, ammonia is toxic to the body.

A process in your liver converts the ammonia into urea. This is less harmful and can be removed from your body safely in the urine. This process is called the Urea Cycle and involves several important steps using different enzymes. The Urea Cycle Disorders occur if there is a lack of any of these enzymes due to a genetic problem. A reduced level of enzymes mean that your body cannot get rid of the excess ammonia allowing it to build up and become harmful, especially to the brain.

If you have this disorder, your body does not produce enough of an enzyme called argininosuccinate synthetase. This leads to a build-up of ammonia and citrulline in the blood

How common is it?

We do not know exactly how common this disorder is, but it is estimated to affect 1 person in every 57,000. Collectively, the Urea Cycle Disorders affect between 1 person in every 8,000 to 1 person in every 44,000.

What are the signs and symptoms?

The severity of the disorder and the age of onset vary greatly. There are different forms of Citrullinaemia type I. These forms are not clear-cut and are only based on when and how you or your child develop symptoms.

  • The classic form which begins in newborn babies. This is the most severe form.
  • The non-classic form which is milder and begins in infancy or later
  • A form which does not have symptoms or high levels of ammonia in the blood
  • A form in which women have the onset of severe symptoms during pregnancy or in the period after birth (postpartum).

In the severe form of Citrullinaemia symptoms begin soon after birth, presenting with a crisis. There are often no problems during pregnancy. Problems appear to begin when the baby starts taking milk and the body is unable to cope with the protein. Symptoms of the crisis can include:

  • refusal to feed
  • vomiting
  • lethargy
  • irritability
  • a lack of muscle tone
  • an enlarged liver
  • breathing difficulties
  • seizures
  • accumulation of fluid in the brain

Symptoms of the crisis rapidly progress and quickly become life-threatening. Unless this disorder is diagnosed and managed quickly it can be fatal. Children with the severe form often have long-term neurological problems.

If you have the non-classic form, signs and symptoms may be less severe and appear later in life. Symptoms happen in episodes. Older children and adults often become extremely ill after a viral illness or after they have had a lot of protein. You may have noticed your child being a fussy eater when it came to foods containing protein.

Symptoms of the non-classic form may include:

  • vomiting
  • poor appetite
  • poor developmental progress
  • episodes of lethargy
  • ataxia
  • liver problems

You may not get all the symptoms listed, or you may have other symptoms. There are a lot of variations. If left untreated, symptoms can progress to coma and become life-threatening.

If you have this disorder you have a very high risk of a crisis happening again. Crises can be triggered by illness or infection, long periods without food, poor management of the disorder, or other causes of stress or trauma. There are also certain drugs that trigger crises

How is it diagnosed?

This disorder is usually diagnosed when the first crisis occurs. Blood tests show high levels of ammonia and further blood and urine tests will be needed to confirm diagnosis. Early diagnosis and management are vital.

Can it be treated?

Citrullinaemia is a lifelong disorder. The optimal aim of managing this disorder is to manage and maintain “safe” levels of ammonia in the blood, help to promote the removal of ammonia from the body through alternative pathways and to stop any increase in ammonia which can be toxic.

To do this you can do the following:

  • Follow a special low-protein diet – Your low-protein diet will be put in place by a specialist dietitian. A carefully balanced diet is necessary to ensure that your body receives the right amounts of calories and essential amino acids. Therefore, any dietary changes must be made by a specialist dietitian who will aim to maintain the correct nutritional balance for you. This will be regularly reviewed. You may be advised to take specialist dietary supplements which are produced especially for this disorder to help ensure the correct level of protein is maintained.
  • Take your medications – Sodium phenylbutyrate is the main medication that is currently used in the management of Urea Cycle Disorders. Sodium benzoate is also used in some patients, either taken on its own or used with Sodium phenylbutyrate. Both medications help to prevent high ammonia levels in the blood (hyperammonaemia). Antacids are sometimes prescribed to counteract any gastrointestinal side effects of drug treatment such as reflux or stomach aches.
  • Follow your emergency regimen – when you receive your diagnosis you will be given an emergency regimen explaining what to do if you or your child becomes ill. This includes getting bugs such as vomiting, diarrhoea and fever. Glucose polymer (energy rich drinks) are given regularly during the illness. The most common of these are Maxijul, Polycal or SOS which are all available on prescription and you will be given advice on how to use them. If you or your child are unable to tolerate these drinks, continue to be ill and/or develop diarrhoea then you will need to be admitted to hospital as soon as possible. You will be given an emergency contact number to ring. However, if this is unavailable you must go to your nearest hospital’s accident and emergency (A&E) department for treatment.
  • Attend your appointments – Regular appointments are vital. You will need to have frequent blood tests to monitor this disorder. Your specialist or dietitian will review your current treatments and make any adjustments if needed. You may also need to see other specialists or community care teams, depending on your needs.

If a hospital visit is needed, a glucose solution will be given directly through the vein. You will also be given medications that help the body to get rid of ammonia. If this does not appear to work, you will be given haemodialysis. Haemodialysis works by filtering your blood via a machine and removes the ammonia before returning your blood to your body.

In some cases, if you or your child have feeding problems, then a gastrostomy tube (a tube inserted through the stomach wall) or a nasogastric tube (manually inserted through the nose into the stomach) may be recommended.

Liver transplants have been used in the treatment of this condition but must be carefully considered and are only available if other treatment options have failed.

The prognosis depends on how severely you are affected. Babies with the severe form have a poor prognosis. However, if the disorder is diagnosed quickly and the correct treatment given rapidly, then the prognosis improves. Long episodes in coma due to high levels of ammonia are likely to result in long-term neurological damage. Special care will be taken to avoid this during any hospital visit.

Do my family need to be tested?

Citrullinaemia can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.

Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inherited Citrullinaemia. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own.

Diagram showing the autosomal recessive inheritance pattern.


Relevant Organisations


References are available on request. Please contact us by phoning 0845 241 2173 or emailing [Resource Library No: CAP005].

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