Diagnosis and Testing
How do I get my child tests for argininosuccinic aciduria?
Argininosuccinic aciduria can be diagnosed after a positive result from newborn screening. In the United States, all 50 states test for this disorder. 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 another urea cycle disorder called argininosuccinate synthetase deficiency. 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 on infants with argininosuccinic aciduria. 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.
If you believe your child may have argininosuccinic aciduria, talk to your pediatrician or a genetic counselor about your concerns. They can help decide if testing is right for you, and can order this testing if necessary. 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.
Nagamani SCS, Erez A, Lee B. Argininosuccinate Lyase Deficiency. GeneReviews website. Accessed July 1, 2017. https://www.ncbi.nlm.nih.gov/books/NBK51784
Argininosuccinic Aciduria. The National Organization for Rare Disorders website. Accessed July 1, 2017. https://rarediseases.org/rare-diseases/argininosuccinic-aciduria
Haberle J. Argininosuccinic aciduria. OrphaNet website. Accessed July 1, 2017. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=23