Children and Youth with Special Health Needs (CYSHN)

Citrullinemia Type I (CIT-I)

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Condition Information

Treatment Options: Taking Action

Family Support Resources

CONDITION INFORMATION

This fact sheet has general information about citrullinemia type I (CIT-I). Every child is different and some of these facts may not apply to your child specifically. Certain treatments may be recommended for some children but not others. Children with CIT-I should be followed by a metabolic doctor in addition to their primary doctor.

What is CIT-I?

CIT-I is one type of amino acid disorder. People with this condition cannot remove ammonia from the body. Ammonia is a harmful substance. It is made when protein and its building blocks, amino acids, are broken down for use by the body.

Amino Acid Disorders:

Amino acid disorders (AAs) are a group of rare inherited conditions. They are caused by enzymes that do not work properly.

Protein is made up of smaller building blocks called amino acids. A number of different enzymes are needed to process these amino acids for use by the body. Because of missing or non-working enzymes, people with amino acid disorders cannot process certain amino acids. These amino acids, along with other toxic substances, then build up in the body and cause problems.

The symptoms and treatment vary between different amino acid disorders. They can also vary from person to person with the same amino acid disorder. See the fact sheets for each specific amino acid disorder.

Amino acid disorders are inherited in an autosomal recessive manner and affect both males and females.

What causes CIT-I?

CIT-I is one of a small number of conditions called “urea cycle disorders” (UCD).

It occurs when an enzyme called “argininosuccinate synthetase” (ASAS), is either missing or not working properly. This enzyme’s job is to help break down certain amino acids and to remove ammonia from the body.

When ASAS is not working, an amino acid called citrulline builds up in the blood. Ammonia and other harmful substances also build up. This causes brain damage. If not treated, excess ammonia in the blood can cause death.

Citrullinemia Diagram

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What causes the ASAS enzyme to be absent or not working correctly?

Genes tell the body to make various enzymes. People with CIT-I have a pair of genes that do not work correctly. Because of the changes in this pair of genes, the ASAS enzyme either does not work properly or is not made at all.

How is CIT-I inherited?

CIT-I is inherited in an autosomal recessive manner. It affects both boys and girls equally.

Everyone has a pair of genes that make the ASAS enzyme. In children with CIT-I, neither of these genes works correctly. These children inherit one non-working gene for the condition from each parent.

Parents of children with CIT-I rarely have the disorder. Instead, each parent has a single non-working gene for CIT-I. They are called carriers. Carriers do not have the condition because the other gene of this pair is working correctly.

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have CIT-I. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.

Autosomal Recessive Inheritance chart

Genetic counseling is available to families who have children with CIT-I. Genetic counselors can answer your questions about how the condition is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a genetic counselor.

Is genetic testing available?

Genetic testing for CIT-I is available. Genetic testing, also called DNA testing, looks for changes in the pair of genes that cause the condition. Ask your metabolic doctor or genetic counselor whether DNA testing is available to your family.

DNA testing is not necessary to diagnose your child. However, it can be helpful for carrier testing or prenatal diagnosis, discussed below.

What other testing is available?

Special tests on blood, urine, or skin samples can be done to confirm CIT-I. Talk to your metabolic doctor if you have questions about this type of testing.

Can you test during pregnancy?

If both gene changes have been found in the child with CIT-I, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or amniocentesis. CVS stands for Chorionic Villus Sampling, which is a special test done early in pregnancy. During CVS, a small sample of the placenta is removed for genetic testing.

If DNA testing would not be helpful, an enzyme test can be done on cells from the fetus. The sample needed is obtained by a procedure called fetal blood sampling. Again, the sample needed for this test is obtained by either CVS or amniocentesis.

Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.

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Can other members of the family have CIT-I or be carriers?

Having CIT-I
The brothers and sisters of a baby with CIT-I have a chance of being affected, even if they haven’t had symptoms. Finding out whether other children in the family have the condition is important because early treatment can prevent serious health problems. Talk to your metabolic doctor or genetic counselor about testing your other children.

CIT-I carriers
Brothers and sisters who do not have CIT-I still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done in people over 18 years of age.

Each of the parents' brothers and sisters has a 50% chance to be a carrier. It is important for other family members to be told that they could be carriers. There is a small chance they are also at risk to have children with CIT-I.

When both parents are carriers, newborn screening results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn screening.

Can other family members be tested?

Diagnostic testing
Brothers and sisters of a child with CIT-I can be tested using blood, urine, or skin samples.

Carrier testing
If both gene changes have been found in your child, other family members can have genetic testing to see if they are carriers.

If DNA testing would not be helpful, other methods of carrier testing may be available. Your metabolic doctor or genetic counselor can answer your questions about carrier testing.

How many people have CIT-I?

This is a rare condition. About one in every 57,000 babies in the United States is born with CIT-I.

Does CIT-I happen more frequently in a certain ethnic group?

The classic form of CIT-I occurs in all ethnic groups around the world.

Does CIT-I go by any other names?

CIT-I is sometimes also called:

  • Citrullinemia (classic form)
  • Argininiosuccinate synthetase deficiency
  • Arginininosuccinic acid synthetase deficiency
  • AS deficiency
  • ASS deficiency
  • Citrullinuria
  • CTLN1

The adult-onset form of CIT-I is also called:

  • Late-onset citrullinemia

A disorder which was originally thought to be related to CIT-I but is now known to be a separate disorder is called:

  • Citrullinemia, Type II
  • Citrin Deficiency

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TREATMENT OPTIONS: TAKING ACTION

What is the treatment for CIT-I?

Your baby's primary doctor will work with a metabolic doctor and a dietician to care for your child.

Prompt treatment is needed to prevent the build-up of ammonia. You should start treatment as soon as you know your child has this condition.

The following are treatments often recommended for babies and children with CIT-I:

1.

Low-protein diet and/or special medical foods and formula
Most children need to eat a diet made up of very low-protein foods, special medical foods, and sometimes a special formula. Your dietician will create a food plan that contains the right amount of protein, nutrients, and energy to keep your child healthy. The food plan should be continued throughout your child’s life.

Low-protein diet
The most effective treatment is a low-protein diet. Foods that need to be avoided or strictly limited include:

  • milk, cheese, and other dairy products
  • meat and poultry
  • fish
  • eggs
  • dried beans and legumes
  • nuts and peanut butter

Eating foods high in protein can cause ammonia to build up in the blood, resulting in severe illness. Many vegetables and fruits have only small amounts of protein and can be eaten in carefully measured amounts.

Do not remove all protein from the diet. Your child still needs a certain amount of protein for normal growth and development. Any changes in the diet should be made under the guidance of a dietician.

Medical foods and formula
There are medical foods such as special low-protein flours, pastas, and rice made especially for people with amino acid disorders.

Your baby may need to drink a special formula that contains the correct amount of nutrients and amino acids. Your metabolic doctor and dietician will decide whether your child needs this formula.

Your child’s exact food plan will depend on many things such as his or her age, weight, and general health. Your dietician will fine-tune your child’s diet over time. Any diet changes should be made under the guidance of a dietician familiar with CIT-I.
2.

Medication
There are certain medications that can help the body get rid of ammonia. Your metabolic doctor will decide whether your child needs these medications, which ones, and how much to use.

During episodes of high ammonia, children need to be treated in the hospital. Medications to remove ammonia are often given by IV. Dialysis is sometimes needed to remove ammonia from the blood.

An amino acid called arginine is often given by mouth to help prevent ammonia build-up. Your doctor will tell you whether your child needs arginine and how much to use. Do not use any supplements or medications without checking with your doctor.
3. Blood tests
Your child will need to have regular blood tests to measure amino acid and ammonia levels. Your child’s diet and medication may need to be adjusted based on blood test results.
4.

Call your doctor at the start of any illness:
For some babies and children with CIT-I, even minor illness can cause high ammonia levels. In order to prevent problems, call your doctor right away when your child has any of the following:

  • loss of appetite
  • low energy or extreme sleepiness
  • vomiting
  • fever
  • infection or illness
  • behavior or personality changes
  • difficulty walking or balance problems

Children with symptoms of high blood ammonia often need to be treated in the hospital. Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child’s care.

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What happens when CIT-I is treated?

With prompt and lifelong treatment, children with CIT-I can often live healthy lives with typical growth and learning. Early treatment can help prevent high ammonia levels.

Even with treatment, some children still have episodes of high ammonia. This can result in brain damage. This can cause lifelong learning problems, mental retardation or spasticity.

If CIT-I is not treated, what problems occur?

Normally, the body changes ammonia into a substance called “urea”. Urea is then safely removed in the urine. If ammonia is not changed to urea, high levels build up in the blood. This can be very harmful. If ammonia levels stay high for too long, severe brain damage can occur.

The symptoms, and the age they start, vary from person to person. There are two main forms of this condition. The most common is called “classic”. It usually starts in infancy. There are also milder forms that start later in infancy or childhood. There is also a rare adult form more common in people from Japan.

Classic CIT-I
Infants seem healthy at birth but quickly develop symptoms. Within a few days of life, babies will have high levels of ammonia in their blood. Some of the first symptoms of high blood ammonia are:

  • poor appetite
  • extreme sleepiness or lack of energy
  • irritability
  • vomiting

If not treated, high ammonia levels cause:

  • muscle weakness
  • decreased or increased muscle tone
  • breathing problems
  • problems staying warm
  • seizures
  • swelling of the brain
  • coma, and sometimes death

Other effects of CIT-I can include:

  • poor growth
  • enlarged liver
  • learning delays or mental retardation

Without treatment, most babies die within the first few weeks of life.

Milder forms
In the milder forms, symptoms start later in infancy or childhood. Symptoms in untreated children can include:

  • poor growth
  • dry, brittle hair
  • hyperactivity
  • behavior problems
  • learning problems or mental retardation
  • avoidance of meat and other high-protein foods
  • spasticity
  • stroke
  • episodes of high levels of ammonia in the blood

Episodes of high blood ammonia often happen:

  • after going without food for long periods of time
  • during illness or infection
  • after high-protein meals

Some of the first symptoms of high blood ammonia in children are:

  • poor appetite
  • severe headache
  • vomiting
  • extreme sleepiness or lack of energy
  • slurred speech
  • poor coordination or balance problems

If not treated, children with high blood ammonia levels may develop:

  • breathing problems
  • swelling of the brain
  • seizures
  • coma, sometimes leading to death

Some people have very mild or no symptoms and are only found to be affected after a brother or sister is diagnosed.

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FAMILY SUPPORT RESOURCES

Where can I find more information?

Minnesota Pediatric Metabolic Providers List

Medically Prescribed Formula: a table that provides a list of commonly prescribed medical foods and formulas and /or medication for this disorder.

National Library of Medicine Genetics Home Reference: Citrullinemia
http://ghr.nlm.nih.gov/condition/citrullinemia

National Urea Cycle Disorders Foundation
http://www.nucdf.org/

CLIMB (Children Living with Inherited Metabolic Diseases)
http://www.climb.org.uk

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For additional genetics information and resources:

More help available from Children and Youth with Special Health Needs (CYSHN):

We would like to acknowledge the Star G Project. The information on the fact sheet was obtained from the Star G Project. For the most up-to-date information on the disorder please visit their web site at http://www.newbornscreening.info. Each fact sheet was extensively reviewed by family support groups, metabolic specialists across the country and the Star G steering committee.

THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content, including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET.
Updated Wednesday, 25-Jul-2012 16:54:40 CDT