General Condition Information
- Argininosuccinate synthetase deficiency (Citrullinemia)
- Citrullinemia I
- Citrullinemia I (ASA synthetase def)
- Citrullinemia type I
- Citrullinemia type I (Argininosuccinate synthetase deficiency)
- Citrullinemia, type 1 or ASA Synthetase deficiency
- Citrullinemia, type 1 or ASA synthetase deficiency
- Citrullinemia, type I or ASA Synthetase deficiency
What is Citrullinemia, type I
Citrullinemia, type I is an inherited (genetic) condition that prevents the body from removing ammonia properly. Ammonia is a waste product produced when the body breaks down protein.
Citrullinemia, type I occurs when an enzyme called arginosuccinate synthase I doesn’t work correctly. You need arginosuccinate synthase I for a process in your body called the urea cycle. The urea cycle helps remove ammonia from the body.
In citrullinemia, type I, this enzyme is missing or is not made correctly. If your baby doesn’t have enough working arginosuccinate synthase I enzyme, ammonia builds up.
High levels of ammonia are very toxic to the body, especially the brain and nerves. If untreated, damage to the brain and nerves leads to the signs and symptoms of the condition. In severe cases, this condition can lead to coma or death if not treated early.
Newborn Screening and Follow-Up
Newborn screening for citrullinemia, type I is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures how much of a substance called citrulline is in your baby’s blood. When the urea cycle is not working well, citrulline builds up. Babies with high levels of citrulline might have citrullinemia, type I.
If your baby’s blood spot screening result for citrullinemia, type I is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans. An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood and/or urine tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems very soon after birth if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition are rare. However, screening samples collected too early (before the baby is 24 hours old) may affect the results of screening.
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs of citrullinemia, type I often appear shortly after birth (within a few days of birth). Rarely, some babies have a mild type of citrullinemia, type I where signs do not start until childhood. These signs may be triggered by eating foods high in protein, going a long time without eating (prolonged fasting), illnesses, and infections.
Signs of the condition may include the following:
The condition is caused by a change in the ASS1 gene. This gene gives your body instructions for making the enzyme arginosuccinate synthase I. This enzyme helps the urea cycle remove the ammonia produced when your body breaks down proteins.
Without a working ASS1 gene, your baby cannot make enough working enzyme. As a result, their body has trouble getting rid of ammonia. High levels of ammonia are very dangerous.
- Citrullinemia, type I is an autosomal recessive condition. Babies inherit it when each parent passes down a nonworking ASS1 gene to their baby. Only babies with two nonworking ASS1 genes—one from the mom and one from the dad—have this condition.
- People with one working copy and one nonworking copy of the ASS1 gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the ASS1 gene, they have a 1 in 4 chance of having a child with citrullinemia, type I.
- Carriers for citrullinemia, type I often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with citrullinemia, type I.
- Parents who already have a child with citrullinemia, type I still have a 1 in 4 chance of having another child with citrullinemia, type I. This 1 in 4 chance stays the same for all future children.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Drugs that help remove ammonia from the body
- Diet low in protein
- Arginine supplements to help lower ammonia levels
- Liver transplant
Children who receive early and ongoing treatment for citrullinemia, type I can have healthy growth and development.