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Carbamoylphosphate Synthetase I Deficiency via the CPS1 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
CPS1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11829CPS181479 81479,81479 $990 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 platform).

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

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

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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.


Genetic Counselors


  • 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 I deficiency (CPS1D; OMIM 237300), argininosuccinate synthetase deficiency (OMIM 215700), argininosuccinate lyase deficiency (OMIM 207900), and arginase deficiency (OMIM 207800). Two clinical presentations of CPS1D are recognized: an early-onset form (Suzuki et al. Eur J Pediatr 145:406-408, 1986) and a delayed-onset form (Batshaw. Ann Neurol 35:133-141, 1994). Individual cases of the delayed-onset form have been reported to be induced by valproic acid (Verbiest et al. Acta Neurol Scand 86:275-279, 1992), childbirth (Wong et al. Ann Intern Med 120:216-217, 1994), or increased protein intake (Martinez et al. Mol Genet and Metab 101:311-323, 2010). Patients with CPS1D present with irritability and hyperammonemia leading to coma and death if untreated. Severe cases have been shown to have absent CPS1 enzyme activity (Finckh et al. Hum Mutat 12:206-211, 1998). A treatment regimen of intravenous sodium benzoate, sodium phenylacetate and arginine; nitrogen-free intravenous alimentation; and, when other measures failed, dialysis was found to be effective at treating hyperammonemia due to CPS1D (Brusilow et al. New Eng J Med 310:1630-1634, 1984). Carbamoyl phosphate synthetase I requires N-acetyl-glutamate (NAG) as a cofactor and produces carbamoyl phosphate from ammonia and carbon dioxide. Deficiency of N-acetyl-glutamate synthase (NAGS; OMIM 237310) results in clinical sequelae indistinguishable from that of CPS1D (Haberle et al. Hum Mut 21:593-597, 2003; Caldovic et al. Hum Mut 28:754-759, 2007).


Hyperammonemia due to carbamoyl phosphate synthetase I deficiency is an autosomal recessive disorder. The majority of pathogenic CPS1 variants are missense variants; however, nonsense, splice site variants, and gross deletions are known as well (Martinez et al. Mol Genet and Metab 101:311-23, 2010; www.hgmd.org).

Clinical Sensitivity - Sequencing with CNV PGxome

The incidence of CPS1D has been estimated at 1:62,000 in the USA (Brusilow and Maestri Adv Pediatr 43:127-170, 1996). Variants in CPS1 were identified in 16 of 18 Japanese patients with a clinical diagnosis of CPS1D (Kurokawa et al. J Hum Genet 52:349-354, 2007). Variants in the NAGS gene (OMIM 608300) should be considered in patients with a high index of suspicion who have normal CPS1 enzyme activity or a normal CPS1 sequencing result.

Testing Strategy

This test provides full coverage of all coding exons of the CPS1 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

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 (Summar, GeneReviews, 2011). 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). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CPS1.


Official Gene Symbol OMIM ID
CPS1 608307
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Congenital Hyperammonemia, Type I AR 237300

Related Test

Urea Cycle Disorders Panel


  • Batshaw, M. L. (1994). "Inborn errors of urea synthesis." Ann Neurol 35(2): 133-41. PubMed ID: 7906500
  • Brusilow, S. W., et.al. (1984). "Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis." N Engl J Med 310(25): 1630-4. PubMed ID: 6427608
  • Brusilow, S. W., Maestri, N. E. (1996). "Urea cycle disorders: diagnosis, pathophysiology, and therapy." Adv Pediatr 43: 127-70. PubMed ID: 8794176
  • Caldovic, L., et.al. (2007). "Mutations and polymorphisms in the human N-acetylglutamate synthase (NAGS) gene." Hum Mutat 28(8): 754-9. PubMed ID: 17421020
  • Finckh, U., et.al. (1998). "Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1." Hum Mutat 12(3): 206-11. PubMed ID: 9711878
  • Haberle, J., et.al. (2003). "Mutation analysis in patients with N-acetylglutamate synthase deficiency." Hum Mutat 21(6): 593-7. PubMed ID: 12754705
  • Kurokawa, K., et.al. (2007). "Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency." J Hum Genet 52(4): 349-54. PubMed ID: 17310273
  • Marshall L Summar (2011). "Urea Cycle Disorders Overview." PubMed ID: 20301396
  • Martinez, A. I., et.al. (2010). "Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1 deficiency." Mol Genet Metab 101(4): 311-23. PubMed ID: 20800523
  • Suzuki, Y., et.al. (1986). "Carbamyl phosphate synthetase I deficiency with no detectable mRNA activity." Eur J Pediatr 145(5): 406-8. PubMed ID: 3792387
  • Verbiest, H. B., et.al. (1992). "Carbamyl phosphate synthetase-1 deficiency discovered after valproic acid-induced coma." Acta Neurol Scand 86(3): 275-9. PubMed ID: 1414247
  • Wong, L. J., et.al. (1994). "Postpartum coma and death due to carbamoyl-phosphate synthetase I deficiency." Ann Intern Med 120(3): 216-7. PubMed ID: 8273985


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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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