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Test Code UCDP Urea Cycle Disorders Gene Panel, 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.

 

Customization of this panel and single gene analysis for any gene present on this panel is available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

 

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


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

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube: Lavender top (EDTA) or yellow top (ACD)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin (Eagle's minimum essential medium with 1% penicillin and streptomycin).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblast

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 (formerly Ahlstrom 226) filter paper, or blood spot collection card

Specimen Volume: 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect Dried Blood Spot Samples.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

2. For collection instructions, see Blood Spot Collection Instructions.

3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777).

4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800).

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.


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:

-Informed Consent for Genetic Testing (T576)

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

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

3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.

Secondary ID

608020

Useful For

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

Method Name

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

Reporting Name

Urea Cycle Disorders Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Reject Due To

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

Clinical Information

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 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) 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 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 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

An interpretive report will be provided.

Interpretation

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

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated to be over 99% for single nucleotide variants, over 94% for deletions-insertions (delins) less than 40 base pairs (bp), and over 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-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 evaluated by 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. See Targeted Genes and Methodology Details for Urea Cycle Disorders Gene Panel for details regarding the targeted genes analyzed and the specific gene regions not routinely covered. (Unpublished Mayo method)

 

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

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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

CPT Code Information

81443

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
UCDP Urea Cycle Disorders Gene Panel 105267-9

 

Result ID Test Result Name Result LOINC Value
608644 Test Description 62364-5
608645 Specimen 31208-2
608646 Source 31208-2
608647 Result Summary 50397-9
608648 Result 82939-0
608649 Interpretation 69047-9
608650 Resources 99622-3
608651 Additional Information 48767-8
608652 Method 85069-3
608653 Genes Analyzed 48018-6
608654 Disclaimer 62364-5
608655 Released By 18771-6

Day(s) Performed

Varies

Testing Algorithm

For skin biopsy and cultured fibroblast specimens, fibroblast culture will be added at an additional charge. If viable cells are not obtained, the client will be notified.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No