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Ornithine Transcarbamylase Deficiency via the OTC 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
OTC 81405 81405,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9723OTC81405 81405,81479 $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 hyperammonemia, encephalopathy, and respiratory alkalosis. Five clinical disorders have been described involving defective urea cycle enzymes: ornithine transcarbamolase deficiency (OMIM 311250), carbamoyl phosphate synthetase I deficiency (OMIM 237300), argininosuccinate synthetase deficiency (OMIM 215700), argininosuccinate lyase deficiency (OMIM 207900), and arginase deficiency (OMIM 207800). Ornithine transcarbamylase (OTC) functions in the liver to generate citrulline from ornithine and carbamoyl phosphate, thus recycling free ammonia. Deficiency of this enzyme leads to elevated ammonia and subsequent ammonia intoxication. Clinical symptoms of hyperammonemia due to OTC deficiency (OMIM 311250) can appear in the neonatal period in patients with significant enzyme deficiency or as late as adulthood in individuals with partial enzyme deficiency (Finkelstein et al. J Pediat 117:897-902, 1990; Drogari et al. Arch Dis Child 63:1363-1367, 1988). Untreated infants develop cerebral edema leading to lethargy, diminished appetite, seizures, and coma. Patients presenting after the neonatal period may demonstrate irritability, vomiting, lethargy, and coma, especially after a high protein meal, or while fasting or during an infection (Oizumi et al. Clin Genet 25:538-542, 1984).


Hyperammonemia due to ornithine transcarbamylase (OTC) deficiency is an X-linked recessive disorder. Although most patients are males, carrier females can experience serious symptoms early in life (Rowe at al. New Eng J Med 314:541-547, 1986) or in adulthood (Gilchrist and Coleman Ann Intern Med. 106:556-558, 1987). Approximately 15% of carrier females develop hyperammonemia (Brusilow Prog Liver Dis 13:293-309, 1995). Over 300 OTC variants have been reported (Yamaguchi et al. Hum Mut 27:626-632, 2006). The majority are missense; however, many nonsense and splice site variants are known as well. Tuchman (Hum Mut 2:174-178, 1993) reported that approximately 10 to 15% of all variants associated with OTC deficiency were large deletions involving all or part of the OTC gene. By array CGH, Shchelochkov et al. (Mol Genet and Metab 96:97-105, 2009) found deletions in half of their patients with normal OTC gene sequencing results.

Clinical Sensitivity - Sequencing with CNV PGxome

Yamaguchi et al. (Hum Mut 27:626-632, 2006) reported that variants could be found in approximately 80% of patients. In a study of 341 OTC variants, the same authors found that 43% were associated with neonatal onset, 20% with later onset in males, and 35% with manifesting females. Array CGH should be considered in all patients with normal sequencing results to rule out a deletion.

Testing Strategy

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

This testing also includes coverage for the following intronic or other non-coding OTC variants, as well as ~10 bp of adjacent sequence: c.-366A>G, c.540+265G>A, c.867+1126A>G and c.1005+1091C>G.

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, 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, 2005). 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).


Official Gene Symbol OMIM ID
OTC 300461
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Ornithine Carbamoyltransferase Deficiency XL 311250

Related Test

Urea Cycle Disorders Panel


  • Brusilow, S. W. (1995). "Urea cycle disorders: clinical paradigm of hyperammonemic encephalopathy." Prog Liver Dis 13: 293-309. PubMed ID: 9224507
  • Drogari, E., Leonard, J. V. (1988). "Late onset ornithine carbamoyl transferase deficiency in males." Arch Dis Child 63(11): 1363-7. PubMed ID: 3202644
  • Finkelstein, J. E., et.al. (1990). "Late-onset ornithine transcarbamylase deficiency in male patients." J Pediatr 117(6): 897-902. PubMed ID: 2246687
  • Gilchrist, J. M., Coleman, R. A. (1987). "Ornithine transcarbamylase deficiency: adult onset of severe symptoms." Ann Intern Med 106(4): 556-8. PubMed ID: 3826955
  • Marshall L Summar (2011). "Urea Cycle Disorders Overview." PubMed ID: 20301396
  • Oizumi, J., et.al. (1984). "Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium." Clin Genet 25(6): 538-42. PubMed ID: 6733950
  • Rowe, P. C., et.al. (1986). "Natural history of symptomatic partial ornithine transcarbamylase deficiency." N Engl J Med 314(9): 541-7. PubMed ID: 3945292
  • Shchelochkov, O. A., et.al. (2009). "High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH." Mol Genet Metab 96(3): 97-105. PubMed ID: 19138872
  • Tuchman, M. (1993). "Mutations and polymorphisms in the human ornithine transcarbamylase gene." Hum Mutat 2(3): 174-8. PubMed ID: 8364586
  • Yamaguchi, S., et.al. (2006). "Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene." Hum Mutat 27(7): 626-32. PubMed ID: 16786505


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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