Argininemia is inherited in an autosomal recessive pattern. Normally a person has two functional ARG1 genes. In people with argininemia, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with argininemia 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 argininemia do not typically have symptoms.
Untreated, the first symptom of argininemia is typically slowed growth starting at age one to three years followed by spasticity and loss of developmental milestones.
- Incidence: The overall incidence is approximately 1 in 300,000 to 1 in 1,000,000.
- New YorkState Method of Screening (First Tier): Screening for argininemia is accomplished by measuring arginine 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. In addition, the screen may be within acceptable limits in some patients with argininemia because arginine may not be elevated until 4-5 days of age in some cases.
- Interpretation/reporting of data: Results are reported as within acceptable limits, 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 argininemia are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of argininemia.
Diagnostic testing may include quantification of plasma amino acids, ammonia, arginase enzyme and molecular genetic testing of the ARG1 gene.
Treatment is usually a protein restricted diet and medication to remove nitrogen from the body (sodium benzoate and sodium phenylbutyrate). The specialized diet includes drinking an arginine-free protein formula. 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.
Prognosis is variable and dependent on multiple factors including the severity of disease.
Argininemia is a urea cycle disorder (inherited metabolic disorder).
Argininemia is caused by mutations in the ARG1 gene. Individuals with this disorder are unable to break down the amino acid arginine. The urea cycle happens in the liver to remove nitrogen from the body. The breakdown of arginine is the final step of the urea cycle. Without this step, arginine and ammonia accumulate in the body.