Invitae Elevated Arginine Test


Test description

The Invitae Elevated Arginine Test analyzes ARG1, the gene that is associated with elevated arginine on newborn screening (NBS) or plasma amino acids. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (1 gene)


Alternative tests to consider

The Invitae Urea Cycle Disorders Panel has been designed to provide a broad genetic analysis of this class of disorders. Depending on the individual’s clinical and family history, this broader panel may be appropriate. It can be ordered at no additional cost.

Arginase deficiency

ARG1 encodes arginase, the enzyme that catalyzes the cleavage of arginine to urea and ornithine—the last step of the urea cycle. Arginase deficiency is a urea-cycle disorder, and the accumulation of arginine is the biochemical hallmark of this condition. Unlike other urea-cycle disorders, arginase deficiency is not generally associated with a severe hyperammonemic encephalopathy in the neonatal period because severe hyperammonemia rarely occurs in this condition. Instead, arginase deficiency typically presents later in childhood, between two and four years of age, with predominantly neurological features. Clumsiness, failure to thrive, and short stature may be observed in early childhood; psychomotor deterioration may be seen from three months to four years of age. The disease is slowly progressive relative to other urea-cycle disorders; nevertheless, if it remains untreated, it advances with developmental regression and spasticity.

It is important to note that arginase deficiency is one of the few treatable causes of spastic diplegia.

For patients with symptoms that are consistent with arginase deficiency and a biochemical diagnosis of arginase deficiency, more than 95% will have two pathogenic mutations in the ARG1 gene.

Arginase deficiency is inherited in an autosomal recessive manner.

The estimated incidence of arginase deficiency is 1 in 950,000 newborn screens. It affects 3 in 7,000 institutionalized individuals with mental retardation.

  1. American College of Medical Genetics. NBS ACT Sheet. Increased Arginine. Accessed February 2016.
  2. Häberle, J, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012; 7:32. PMID: 22642880
  3. Jay, A, et al. Case Report of Argininemia: The Utility of the Arginine/Ornithine Ratio for Newborn Screening (NBS). JIMD Rep. 2013; 9:121-4. PMID: 23430558
  4. National Organization for Rare Disorders. Arginase Deficiency. Accessed February 2016.
  5. Naylor, EW, et al. A simple screening test for arginase deficiency (hyperargininemia). J. Lab. Clin. Med. 1977; 89(4):876-80. PMID: 845487
  6. Prasad, AN, et al. Argininemia: a treatable genetic cause of progressive spastic diplegia simulating cerebral palsy: case reports and literature review. J. Child Neurol. 1997; 12(5):301-9. PMID: 9378897
  7. Scaglia, F, Lee, B. Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase I deficiency. Am J Med Genet C Semin Med Genet. 2006; 142C(2):113-20. PMID: 16602094
  8. Sin, YY, et al. Arginase-1 deficiency. J. Mol. Med. 2015; 93(12):1287-96. PMID: 26467175
  9. Summar, ML, et al. The incidence of urea cycle disorders. Mol. Genet. Metab. 2013; 110(1-2):179-80. PMID: 23972786
  10. Uchino, T, et al. Molecular basis of phenotypic variation in patients with argininemia. Hum. Genet. 1995; 96(3):255-60. PMID: 7649538
  11. Wijburg FA, Nassogne MC. Inborn metabolic diseases: diagnosis and treatment. 5th ed. Heidelberg: Springer; 2012. Chapter 20, Disorders of the Urea Cycle and Related Enzymes; p. 297–310.
  12. Wong, D, et al. Arginase Deficiency. 2004 Oct 21. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301338

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ARG1 NM_000045.3