Argininosuccinate Lyase Deficiency via the ASL Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits


Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1181 ASL$970.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
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).

See More

See Less

Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 ASL$990.00 81479 Add to Order
Pricing Comment

# of Genes Ordered

Total Price









Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity
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).

See More

See Less

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).
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.).
Testing Strategy
Argininosuccinate lyase is encoded by exons 2-17 of the ASL gene on chromosome 7q11. This test involves bidirectional DNA Sanger sequencing of all coding exons and splice sites of ASL. The full coding sequence of each exon plus ~10 bp of flanking DNA on either side are sequenced. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known pathogenic variants or to confirm research results.
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).


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


Name Inheritance OMIM ID
Argininosuccinate Lyase Deficiency 207900


Genetic Counselors
  • 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
Order Kits

Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
loading Loading... ×