Argininosuccinic aciduria

In the United States, all 50 states include argininosuccinic aciduria on newborn screening. During routine newborn screening, a tiny sample of blood is taken from the heel of a newborn. This test, called a heel prick or Guthrie test, involves getting a few drops of blood from a pinprick in the newborn's heel. The blood is run through a machine that can detect high levels of citrulline, an amino acid that abnormally builds up in people with argininosuccinic aciduria, and a few other disorders. Sometimes, newborn screening may miss an infant with the disorder, and sometimes there may be a false positive.

Additional tests will be performed to confirm the diagnosis. These tests involve looking at the blood and urine for substances that are abnormally elevated in argininosuccinic aciduria. In a blood sample, ammonia and citrulline may be elevated. High levels of ammonia are characteristic of all urea cycle disorders. Citrulline is an amino acid. Amino acids are building blocks of protein. Citrulline is elevated in the blood of children with argininosuccinic aciduria and argininosuccinate synthetase deficiency (another type of urea cycle disorder). Elevated levels of argininosuccinic acid may also be found in the blood or the urine.

Sometimes, doctors will take a sample of skin tissue. They will test certain cells called fibroblasts to determine the activity of the enzyme argininosuccinic lyase, which is reduced in people with this disorder. This is called an enzyme assay.

Information about newborn screening programs can be found at Save Babies Through Screening Foundation or Baby's First Test.

Infants with argininosuccinic aciduria may be detected through newborn screening (NBS). NBS can detect elevated levels of citrulline in the dried blood spots. Additional tests will be performed to confirm the diagnosis. These tests involve looking at the blood and urine for substances that are abnormally elevated in argininosuccinic aciduria. In a blood sample, ammonia and citrulline may be elevated. High levels of ammonia are characteristic of all urea cycle disorders. Elevated levels of argininosuccinic acid may also be found in the blood or the urine. Sometimes, doctors will take a sample of skin tissue. They will test certain cells called fibroblasts to determine the activity of the enzyme argininosuccinic lyase, which is reduced in people with this disorder. This is called an enzyme assay.

Doctors may also conduct molecular genetic testing. Doctors recommend these tests to help create the most effective treatment plan or allow other family members to have genetic testing done. These tests involve studying the ASL gene for changes (mutations) that cause the disorder. This can include sequence analysis, where a part or sequence of DNA within a gene is examined, deletion/duplication analysis, where missing or extra regions of DNA are looked for within a specific gene, or targeted analysis, where know changes are looked for in the ASL gene. Molecular genetic testing must be done at specialized laboratories.

In a family with argininosuccinic aciduria, tests can be done to see whether other family members are carriers for the disorder. (Carriers do not have symptoms and have one working and one non-working copy of the ASL gene.) However, the specific gene changes in that family needs to be known. If known, all siblings and other at-risk relatives can be tested. Molecular genetic testing, which are tests that look for changes to genes, can be performed. A newborn child in a family with a history of argininosuccinic aciduria should be tested through molecular genetic testing. A genetic counselor or a physician with experience in diagnosing and treating this disorder can provide advice about how a confirmed diagnosis can affect other family members. A listing of medical geneticists can be found at the American College of Medical Genetics and Genomics website and genetic counselors can be found on the National Society of Genetic Counselors website in the United States, and in Canada at the Canadian Association of Genetic Counsellors website.

Some parents may choose to have their child tested for argininosuccinic aciduria before they are born. This is known as prenatal diagnosis. If the gene change(s) that causes argininosuccinic aciduria are known in a family, then molecular genetic testing (which can detect these changes) can be used for prenatal diagnosis. A sample of tissue can be taken from the placenta to test for changes in the ASL gene. This test is called chorionic villus sampling. Another test is called amniocentesis, which involves taking a sample of the amniotic fluid that surrounds and protects a developing fetus. Cells known as amniocytes are taken from the fluid and studied for changes in the ASL gene. There are risks to the unborn baby of doing these tests before birth.

If molecular genetic testing is not possible, doctors can make a prenatal diagnosis through biochemical testing. This testing can detect elevated levels of argininosuccinic acid in amniotic fluid. Doctors can also use chorionic villus sampling or amniocentesis to test for the activity of the argininosuccinate lyase enzyme, which is reduced in infants with argininosuccinic aciduria.

Talk to your doctor or a genetic counselor in your area to discuss the risks and benefits of prenatal diagnosis. Genetic counselors can be found on the National Society of Genetic Counselors website in the United States, and in Canada at the Canadian Association of Genetic Counsellors website.