Test Id : 3MGAP
3-Methylglutaconic Aciduria Panel, Varies
Useful For
Suggests clinical disorders or settings where the test may be helpful
Follow up for abnormal biochemical results suggestive of 3-methylglutaconic aciduria (3-MGA)
Establishing a molecular diagnosis for patients with 3-MGA
Identifying variants within genes known to be associated with3-MGA, 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 17 genes associated with 3-methylglutaconic aciduria: AGK, ATP5F1E, ATPAF2, AUH, CLPB, CPS1, DNAJC19, GFER, HMGCL, HTRA2, OPA3, POLG, SERAC1, SUCLA2, TAZ, TIMM50, TMEM70. See Targeted Genes and Methodology Details for 3-Methylglutaconic Aciduria Panel and Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for 3-methylglutaconic aciduria.
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 |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Method Name
A short description of the method used to perform the test
Sequence Capture and Targeted Next-Generation Sequencing (NGS) 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.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
NextGen Sequencing Test
3-methylglutaconic aciduria
3-MG-CoA-HYDRATASE DEFICIENCY
HMG-CoA lyase deficiency
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Specimen Type
Describes the specimen type validated for testing
Varies
Ordering Guidance
The recommended first-tier biochemical test is urine organic acids; order OAU / Organic Acids Screen, 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 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. 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.
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 spots, 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.
Special Instructions
Library of PDFs including pertinent information and forms related to the test
- Molecular Genetics: Biochemical Disorders Patient Information
- Informed Consent for Genetic Testing
- Blood Spot Collection Card-Spanish Instructions
- Blood Spot Collection Card-Chinese Instructions
- Informed Consent for Genetic Testing (Spanish)
- Blood Spot Collection Instructions
- Targeted Genes and Methodology Details for 3-Methylglutaconic Aciduria Panel
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.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
See Specimen Required
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
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 | ||
Useful For
Suggests clinical disorders or settings where the test may be helpful
Follow up for abnormal biochemical results suggestive of 3-methylglutaconic aciduria (3-MGA)
Establishing a molecular diagnosis for patients with 3-MGA
Identifying variants within genes known to be associated with3-MGA, 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 17 genes associated with 3-methylglutaconic aciduria: AGK, ATP5F1E, ATPAF2, AUH, CLPB, CPS1, DNAJC19, GFER, HMGCL, HTRA2, OPA3, POLG, SERAC1, SUCLA2, TAZ, TIMM50, TMEM70. See Targeted Genes and Methodology Details for 3-Methylglutaconic Aciduria Panel and Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for 3-methylglutaconic aciduria.
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The 3-methylglutaconic acidurias (3-MGA) are a heterogeneous group of metabolic conditions characterized by increased urinary excretion of 3-MGA. Primary 3-MGA type I is an organic aciduria caused by defective leucine catabolism due to variants in 3-methylglutaconyl-CoA hydratase. Four more types of 3-MGA have been described where 3-MGA is a consistent feature. These are characterized by various degrees of mitochondrial dysfunction, very remotely, if at all, linked to leucine degradation and include Barth syndrome (type II), Costeff syndrome (type III), and type V or dilated cardiomyopathy with ataxia) syndrome. The remaining cases (type IV) with increased 3-MGA encompass a variety of disorders affecting mitochondrial function. Genes known to be associated with elevations of 3-MGA are included on this panel.
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 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 the 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 at least one reportable variant in an affected family member would allow for more informative testing of at-risk individuals.
To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratories genetic counselors 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; 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 a specific clinical disorder is suspected, evaluation by alternative methods can be considered.
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. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.
This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.
Deletion/Duplication Analysis:
This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.
This test is not designed to detect low levels of mosaicism or 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.
Genes may be added or removed based on updated clinical relevance. For detailed information regarding gene-specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.
If the patient has had an allogeneic hematopoietic stem cell transplant or a recent heterologous blood transfusion, 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.
Reclassification of Variants:
Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur, the laboratory may issue an amended report.
Variant Evaluation:
Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology 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.
Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. These findings will be carefully reviewed to determine whether they will be 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;17(5):405-424
2. Wortmann SB, Kluijtmans LA, Engelke UF, Wevers RA, Morava E. The 3-methylglutaconic acidurias: what's new?. J Inherit Metab Dis. 2012;35(1):13-22. doi:10.1007/s10545-010-9210-7
3. Manoli I, Venditti CP. Disorders of branched chain amino acid metabolism. Transl Sci Rare Dis. 2016;1(2):91-110. doi:10.3233/TRD-160009
4. Wortmann SB, Duran M, Anikster Y, et al. Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. J Inherit Metab Dis. 2013;36:923-928. doi:10.1007/s10545-012-9580-0
Method Description
Describes how the test is performed and provides a method-specific reference
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), 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.
See Targeted Genes and Methodology Details for 3-Methylglutaconic Aciduria Panel for details regarding the targeted 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 3-Methylglutaconic Aciduria Panel for details regarding the specific gene regions not routinely covered.(Unpublished Mayo method)
Genes analyzed: AGK, ATP5F1E, ATPAF2, AUH, CLPB, CPS1, DNAJC19, GFER, HMGCL, HTRA2, OPA3, POLG, SERAC1, SUCLA2, TAZ, TIMM50, and TMEM70
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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 account representative. 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. It 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.
CPT codes are provided by the performing laboratory.
81443
88233-Tissue culture, skin, solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| 3MGAP | 3-Methylglutaconic Aciduria Panel | 105342-0 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 608812 | Test Description | 62364-5 |
| 608813 | Specimen | 31208-2 |
| 608814 | Source | 31208-2 |
| 608815 | Result Summary | 50397-9 |
| 608816 | Result | 82939-0 |
| 608817 | Interpretation | 69047-9 |
| 608818 | Resources | 99622-3 |
| 608819 | Additional Information | 48767-8 |
| 608820 | Method | 85069-3 |
| 608821 | Genes Analyzed | 48018-6 |
| 608822 | Disclaimer | 62364-5 |
| 608823 | Released By | 18771-6 |