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Argininosuccinate Lyase Deficiency via the ASL 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
9531 ASL 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9531ASL81479 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 (1) hyperammonemia, (2) encephalopathy, and (3) respiratory alkalosis. Five clinical disorders have been described involving defective urea cycle enzymes: ornithine transcarbamolase deficiency (OMIM 311250), carbamoyl phosphate synthetase deficiency (OMIM 237300), argininosuccinate synthetase deficiency (Citrullinemia Type I; OMIM 215700), argininosuccinate lyase deficiency (OMIM 207900), and arginase deficiency (OMIM 207800).

Argininosuccinate lyase deficiency (ASLD) is the second most common urea cycle disorder with an estimated prevalence of 1:70,000 live births and has variable clinical presentation (Tuchman et al. 2008; Nagamani et al. 2012). Severe neonatal-onset of ASLD is characterized by acute life-threatening hyperammonemia, similar to that of other early-onset urea cycle disorders. The presence of hepatomegaly and trichorrhexis nodosa (fragile hair) at the neonatal stage may be suggestive of ASLD. The clinical presentation of late-onset ASLD is characterized by episodic hyperammonemia and/or manifestations unrelated to hyperammonemia. The latter features are unique to ASLD, including neurocognitive deficiencies, impaired liver function, hepatomegaly, liver fibrosis, trichorrhexis nodosa, and hypertension (Tuchman et al. 2008; Nagamani et al. 2012; Ficicioglu et al. 2009). First-line treatments for ASLD are lifelong dietary protein restriction and arginine base supplementation (Erez et al. 2011).

Genetics

Argininosuccinate lyase deficiency is an autosomal recessive disorder that results from pathogenic variants in the ASL gene. Argininosuccinate lyase, which is expressed in a wide variety of tissues, cleaves argininosuccinate to arginine and fumarate in the urea cycle and is the only enzyme generating endogenous arginine in the body (Nagamani et al. 2012). Over 130 different pathogenic variants in the ASL gene have been reported. Missense and nonsense variants are the predominant types, and there is only one gross deletion reported (Balmer et al. 2014; Human Gene Mutation Database). The c.1153C>T variant is a founder mutation in the Finnish population, and the c.1060C>T and c.346C>T variants are two founder mutations commonly present in individuals of Arab ancestry (Nagamani et al. 2012.).

Clinical Sensitivity - Sequencing with CNV PGxome

Sensitivity of this test appears to be very high. Pathogenic variants can be detected in about 90% of patients affected with ASLD via sequence analysis of the ASL coding region (Nagamani et al. 2012).

Gross deletion and duplication variants appear to be rare. Only one large deletion has been reported to date in which exons 2-5 was deleted with a change c.12+651_c.447-233del9609 (Balmer et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the ASL 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).

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

Patients suspected to have ASLD based on clinical and/or biochemical findings (elevated plasma ammonia, elevated argininosuccinic acid in plasma and/or urine). Note: Newborn screening programs use citrulline as a biomarker for detection of ASLD, which is also elevated in patients with citrullinemia type 1, citrullinemia type 2, and pyruvate carboxylase deficiency; therefore, elevated plasma or urine concentration of argininosuccinic acid is necessary to confirm of the diagnosis of ASLD (Nagamani et al. 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ASL.

Gene

Official Gene Symbol OMIM ID
ASL 608310
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Argininosuccinate Lyase Deficiency AR 207900

Related Test

Name
Urea Cycle Disorders Panel

Citations

  • Balmer C, Pandey AV, Rüfenacht V, Nuoffer J-M, Fang P, Wong L-J, Häberle J. 2014. Mutations and Polymorphisms in the Human Argininosuccinate Lyase ( ASL ) Gene. Human Mutation 35: 27–35. PubMed ID: 24166829
  • Erez A, Nagamani SCS, Lee B. 2011. Argininosuccinate lyase deficiency-argininosuccinic aciduria and beyond. Am J Med Genet C Semin Med Genet 157C: 45–53. PubMed ID: 21312326
  • Ficicioglu C, Mandell R, Shih VE. 2009. Argininosuccinate lyase deficiency: longterm outcome of 13 patients detected by newborn screening. Mol. Genet. Metab. 98: 273–277. PubMed ID: 19635676
  • Human Gene Mutation Database (Bio-base).
  • Nagamani SCS, Erez A, Lee B. 2012. Argininosuccinate lyase deficiency. Genet. Med. 14: 501–507. PubMed ID: 22241104
  • Nagamani SCS, Erez A, Lee B. 2012. Argininosuccinate Lyase Deficiency. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 21290785
  • Tuchman M, Lee B, Lichter-Konecki U, Summar ML, Yudkoff M, Cederbaum SD, Kerr DS, Diaz GA, Seashore MR, Lee H-S, McCarter RJ, Krischer JP, et al. 2008. Cross-sectional multicenter study of patients with urea cycle disorders in the United States. Mol. Genet. Metab. 94: 397–402. PubMed ID: 18562231

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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