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Argininemia via the ARG1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11825 ARG1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11825ARG181479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • McKenna Kyriss, PhD

Clinical Features and Genetics

Clinical Features

Urea cycle defects are characterized by hyperammonemia, encephalopathy and respiratory alkalosis (Brusilow and Horwich 2014). Eight clinical disorders have been described involving defective urea cycle enzymes or transporter proteins: N-acetylglutamate synthase deficiency, carbamoyl phosphate synthetase I deficiency, ornithine transcarbamolase deficiency, argininosuccinate synthetase deficiency (also known as citrullinemia type I), argininosuccinate lyase deficiency, arginase deficiency, citrin deficiency (also known as citrullinemia type II) and hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome (Ah Mew et al. 2015). Untreated patients with arginase deficiency develop spastic paraplegia, epileptic seizures, and severe mental retardation (Cederbaum et al. 1977; Wong et al. 2014). Hyperammonemia due to arginase deficiency is usually less severe than that arising from defects in the proximal urea cycle enzymes. Early growth and development are generally normal until ages 1 to 3 years when symptoms begin to be evident (Wong et al. 2014). An arginine restricted diet along with sodium benzoate to scavenge ammonia has been found to be effective treatment (Bernar et al. 1986; Wong et al. 2014).

Genetics

Argininemia is an autosomal recessive disorder caused by pathogenic sequence variants in the ARG1 gene, which is located at chromosome 6q23. ARG1 pathogenic variants are the only known cause of argininemia, and thus far over 50 pathogenic ARG1 sequence variants have been reported in the literature. Missense, nonsense and small deletion variants are the predominant types of disease causing variants in the ARG1 gene, though splice variants, small insertions, duplication and indels, as well as gross deletions, have all been reported (Human Gene Mutation Database).

ARG1 encodes arginase, a liver-specific enzyme that generates urea and ornithine from arginine in the last step of the urea cycle. The ARG1 gene product is also active in red blood cells.

Clinical Sensitivity - Sequencing with CNV PGxome

In patients previously diagnosed with elevated serum arginine and decreased enzyme activity, test sensitivity should be very high. For example, in eleven argininemia patients Uchino et al. (1995) detected 21 of 22 possible mutant alleles. Similarly, Cardoso et al. (1999) detected 2 pathogenic alleles in each of 4 patients, and Carvalho et al. (2012) detected 2 pathogenic alleles in each of 16 patients. Overall, this suggests a clinical sensitivity of ~98%.

Overall, large duplications and deletions appear to be relatively rare in the ARG1 gene. To our knowledge, only two large deletions have been reported in the literature to date (Wang et al. 2012; Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the ARG1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Note that this test includes coverage for the pathogenic deep intronic variant designated c.306-611T>C.

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

A plasma ammonia concentration of 150 μmol/L or higher, associated with a normal anion gap and a normal serum glucose concentration is a strong indication for the presence of a urea cycle defect (Ah Mew et al. 2015). Plasma citrulline levels can differentiate between defects in proximal urea cycle enzymes (low citrulline; OTC and carbamoyl phosphate synthetase) from distal enzymes (high citrulline; argininosuccinate synthetase, argininosuccinate lyase, and arginase). Individuals with elevated serum arginine levels or reduced arginase activity in red cells are candidates for ARG1 testing. Family members of patients known to have ARG1 variants are also good candidates for this test. We will also sequence the ARG1 gene to determine carrier status.

Gene

Official Gene Symbol OMIM ID
ARG1 608313
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Arginase Deficiency AR 207800

Citations

  • Ah Mew N. et al. 2015. Urea Cycle Disorders Overview. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301396
  • Bernar J. et al. 1986. The Journal of Pediatrics. 108: 432-5. PubMed ID: 3950825
  • Brusilow S.W. and Horwich A.L. 2014. Urea Cycle Enzymes. Online Metabolic & Molecular Bases of Inherited Disease, New York, NY: McGraw-Hill.
  • Cardoso M.L. et al. 1999. Human Mutation. 14: 355-6. PubMed ID: 10502833
  • Carvalho D.R. et al. 2012. Gene. 509: 124-30. PubMed ID: 22959135
  • Cederbaum S.D. et al. 1977. The Journal of Pediatrics. 90: 569-73. PubMed ID: 839368
  • Human Gene Mutation Database (Bio-base).
  • Uchino T. et al. 1995. Human Genetics. 96: 255-60. PubMed ID: 7649538
  • Wang J. et al. 2012. Molecular Genetics and Metabolism. 106: 221-230. PubMed ID: 22494545
  • Wong D. et al. 2014. Arginase Deficiency. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle.

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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