Test Catalog

Test Id : UCDP

Urea Cycle Disorders Gene Panel, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Follow up for abnormal biochemical results suggestive of a urea cycle disorder (UCD)

 

Establishing a molecular diagnosis for patients with a UCD

 

Identifying variants within genes known to be associated with UCD, allowing for predictive testing of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 16 genes associated with urea cycle disorders (UCD). This test includes next-generation sequencing to test for variants in the genes indicated: ALDH18A1, ARG1, ARG2, ASL, ASS1, CA5A, CPS1, GLUD1, GLUL, NAGS, OAT, OTC, SLC25A13, SLC25A15, SLC7A7, UMPS. See Method Description for additional details.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for UCD.

 

Additional first tier testing may be considered/recommended.

 

For more information see Advisory Information.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
FIBR Fibroblast Culture Yes No
CRYOB Cryopreserve for Biochem Studies No No

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

Custom Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

No

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Urea Cycle Disorders Gene Panel

Aliases
Lists additional common names for a test, as an aid in searching

NextGen Sequencing Test

Argininemia

Argininosuccinic aciduria

Citrullinemia

Hyperammonemia

Ornithine transcarbamylase (OTC) deficiency

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

The recommended first-tier biochemical tests to screen for urea cycle disorders  are a combination of quantitative plasma amino acids and urinary orotic acid. Order AAQP/ Amino Acids, Quantitative, Plasma and OROT/ Orotic Acid, Random, Urine.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:

-Informed Consent for Genetic Testing  (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies (preferred)

Useful For
Suggests clinical disorders or settings where the test may be helpful

Follow up for abnormal biochemical results suggestive of a urea cycle disorder (UCD)

 

Establishing a molecular diagnosis for patients with a UCD

 

Identifying variants within genes known to be associated with UCD, allowing for predictive testing of at-risk family members

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 16 genes associated with urea cycle disorders (UCD). This test includes next-generation sequencing to test for variants in the genes indicated: ALDH18A1, ARG1, ARG2, ASL, ASS1, CA5A, CPS1, GLUD1, GLUL, NAGS, OAT, OTC, SLC25A13, SLC25A15, SLC7A7, UMPS. See Method Description for additional details.

 

Identification of a pathogenic variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for UCD.

 

Additional first tier testing may be considered/recommended.

 

For more information see Advisory Information.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Urea cycle disorders (UCD) are a group of inherited disorders of nitrogen detoxification that result when any of the enzymes in the urea cycle have reduced or absent activity. These disorders include carbamoylphosphate synthetase I (CPS I) deficiency, ornithine transcarbamylase (OTC) deficiency,  argininosuccinic acid synthetase deficiency (citrullinemia), argininosuccinic acid lyase deficiency (argininosuccinic aciduria), arginase deficiency, the cofactor producer, N-acetyl glutamate synthetase (NAGS) deficiency, and two amino acid transporters, ornithine translocase deficiency (hyperornithinemia, hyperammonemia, homocitrullinuria syndrome: HHH syndrome) and citrin deficiency. The role of the urea cycle is to metabolize and clear waste nitrogen, and defects in any of the steps of the pathway can result in an accumulation of toxic ammonia in the nervous system. The urea cycle is also responsible for endogenous production of the amino acids citrulline, ornithine, and arginine.

 

Infants with a complete urea cycle enzyme deficiency typically appear normal at birth, but they present in the neonatal period with lethargy, seizures, hyper- or hypoventilation, and ultimately coma or death, as a result of elevated ammonia levels. Individuals with partial enzyme deficiency may present later in life, typically following an acute illness or other catabolic stressor. Symptoms may be less severe and may appear as episodes of psychosis, lethargy, cyclical vomiting, and behavioral abnormalities. Patients with impaired ornithine metabolism due to ornithine aminotransferase (OAT) deficiency may present with childhood onset myopia progressing to vision loss in the 4th to 6th decades of life. Patients may or may not have accompanying hyperammonemia but display marked elevations in plasma ornithine.

 

All of the UCD are inherited as autosomal recessive disorders, with the exception of OTC deficiency, which is X-linked. UCD may be suspected with elevated ammonia, normal anion gap, and a normal glucose.

 

This comprehensive gene panel is a helpful tool to establish a diagnosis for patients with suggestive clinical and biochemical features given the broad clinical spectrum and genetic heterogeneity of UCD. Molecular genetic testing can help to distinguish among the conditions and allows for diagnostic confirmation.

 

A combination of biochemical tests including quantitative plasma amino acids (AAQP / Amino Acids, Quantitative, Plasma) and urinary orotic acid (OROT / Orotic Acid, Random, Urine) are recommended as the first-tier test to assess patients for UCD.

 

Acute treatment for UCD consists of dialysis and administration of nitrogen scavenger drugs to reduce ammonia concentration. Chronic management typically involves restriction of dietary protein with essential amino acid supplementation. More recently, liver transplantation has been used with success in treating some patients.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at risk individuals.

 

To discuss the availability of further testing options, for assistance in general test selection, or for assistance in the interpretation of these results, Mayo Clinic Laboratory genetic counselors can be contacted at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions, but assay performance below the minimum acceptable criteria or for failed regions will be noted.  Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If specific clinical disorders are suspected, evaluation by alternative methods can be considered.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, these results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

There may be regions of genes that cannot be effectively amplified for sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This assay will not reliably detect insertions/deletions (indels) of 40 or more base pairs (bp), including Alu insertions, long interspersed nuclear elements (LINES), and short interspersed nuclear elements (SINES). The bioinformatics software pipeline is verified to detect 95% of deletions up to 75 bp and insertions up to 47 bp

 

Additionally, low level mosaic variants may not be detected.

 

This test is not designed to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Reclassification of Variants-Policy:

At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.

 

Variant Evaluation:

Evaluation and categorization of variants is performed using published American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) recommendations as a guideline.(1) Other gene specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported. Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment. Intronic and synonymous sequence variants not predicted to impact splicing or otherwise contribute to disease are not reported.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424

2. Brusilow SW, Horwich AL: Urea cycle enzymes. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill Education; 2019. Accessed October 29, 2020. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225084071&bookid=2709&Resultclick=2

3. Haberle J, Burlina A, Chakrapani A, et al: Suggested guidelines for diagnosis and management of urea cycle disorders: First revision. J Inherit Metab Dis. 2019;1-39. doi: 10.1002/jimd.12100

4. Valle D, Simell O: The hyperornithinemias. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA. eds. The Online Metabolic and Molecular Bases of Inherited DiseaseMcGraw-Hill Education; 2019. Accessed October 29, 2020. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225083672&bookid=2709&Resultclick=2

5. Foshci FG, Morelli MC, Savini S, et al: Urea cycle disorders: A case report of a successful liver transplant and a literature review. World J Gastroenterol. 2015 Apr 7;21(13):4063-4068

6. Ah Mew N, Simpson KL, Gropman AL, et al: Urea cycle disorders overview. In: Adam MP, Ardinger HH, Pagon RA, et al. eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated June 22, 2017. Accessed January 3, /2020. Available at www.ncbi.nlm.nih.gov/books/NBK1217/

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing is performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed. NGS and/or a polymerase chain reaction (PCR)-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed..

 

There may be regions of genes that cannot be effectively amplified for sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria..

 

PCR-based methods and/or Sanger sequencing is used to confirm variants detected by NGS when appropriate.(Unpublished Mayo method)

Genes analyzed: ALDH18A1, ARG1, ARG2, ASL, ASS1, CA5A, CPS1, GLUD1, GLUL, NAGS, OAT, OTC, SLC25A13, SLC25A15, SLC7A7, UMPS

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

3 to 4 weeks

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole Blood: 2 weeks (if available); Extracted DNA: 3 months

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81443

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports