ASA deficiency is inherited in an autosomal recessive pattern. Normally a person has two functional ASL genes. In people with ASA deficiency, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with ASA deficiency typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of ASA deficiency do not typically have symptoms.
There are two forms of ASA deficiency, severe neonatal-onset and late-onset.
Severe neonatal onset: Ammonia is very elevated in the first few days of life, causing vomiting and lethargy. Untreated infants will develop seizures and go into a coma, which may result in death.
Late-onset: Elevated ammonia is triggered by illness or stress in this form. The symptoms may be neurological (developmental delay, intellectual disability, seizures, ADHD), liver disease, coarse, brittle hair and high blood pressure.
- Incidence: The overall incidence is 1 in 70,000.
- New York State Method of Screening (First Tier): Screening for ASA deficiency is accomplished by measuring citrulline by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: Screening for this disorder is not reliable in newborns receiving total parenteral nutrition.
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for ASA deficiency are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of ASA deficiency.
Diagnostic testing may include quantification of plasma amino acids, ammonia, ASL enzyme and molecular genetic testing of the ASL gene.
Treatment is usually a protein restricted diet and supplementation with arginine. Medication may also be given to remove nitrogen from the body (sodium benzoate and sodium phenylbutyrate). If ammonia is very elevated from high protein meals, fasting or illness, in-patient treatment including intravenous fluids, sodium benzoate, sodium phenylbutyrate and dietary management may be required. If these treatments fail, hemodialysis may be needed. There have been reports of liver transplants as a treatment for ASA deficiency.
Prognosis is variable and dependent on multiple factors, including the severity of disease.
Argininosuccinic aciduria (ASA) deficiency is a urea cycle disorder (inherited metabolic disorder).
ASA deficiency is caused by mutations in the ASL gene. The urea cycle removes nitrogen from the body in the form of ammonia. Also during the urea cycle, an essential amino acid, arginine, is processed for use by the body. Individuals with ASA deficiency are unable to remove ammonia or process arginine. The accumulation of ammonia is highly toxic.