Test Catalog

Test Id : DMITO

Mitochondrial DNA Deletion Heteroplasmy, ddPCR, Varies

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

Assessing the heteroplasmy level of previously detected large mitochondrial DNA (mtDNA) deletions.

 

Screening family members for previously detected large mtDNA deletions.

 

This test is not recommended for first tier diagnostic testing for mitochondrial disorders.

 

This test does not assess mtDNA depletion.

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 droplet digital polymerase chain reaction (ddPCR) for confirmation and determination of heteroplasmy levels of previously detected large mitochondrial DNA (mtDNA) deletions.

 

Identification of heteroplasmy for large mtDNA deletions may assist with the diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for mtDNA deletion syndromes.

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 No 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

Droplet Digital Polymerase Chain Reaction (ddPCR)

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

Yes

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

Mitochondrial Deletion Heteroplasmy

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

Chronic progressive external ophthalmoplegia

CPEO

Kearns-Sayre syndrome

Leigh syndrome

Pearson syndrome

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

For diagnosis of a mitochondrial DNA deletion syndrome, the recommended first tier test is MITOP/ Mitochondrial Full Genome Analysis, Next-Generation Sequencing (NGS), Varies.

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.

 

Submit only 1 of the following specimens:

 

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 whole blood specimen in original tube. Do not aliquot.

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

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy. 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: 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: Muscle tissue biopsy

Supplies: Muscle Biopsy Kit (T541)

Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation Sheet.

Specimen Volume: 10-80 mg

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

 

Specimen Type: Snap frozen nerve tissue biopsy

Collection Instructions: Prepare snap frozen tissue biopsy per surgical procedure

Specimen Volume: 0.25-0.5 cm

Specimen Stability Information: Frozen

 

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: 2 to 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient 1 year of age or older is a fingerstick. For infants younger than 1 year, a heel stick should be used. See How to Collect Dried Blood Spot Samples via fingerstick.

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).

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:

-Informed Consent for Genetic Testing (T576)

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

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

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

Blood: 1 mL; Blood spots: 2 spots; Other specimen types: See Specimen Required

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

All specimens will be evaluated at 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

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

Assessing the heteroplasmy level of previously detected large mitochondrial DNA (mtDNA) deletions.

 

Screening family members for previously detected large mtDNA deletions.

 

This test is not recommended for first tier diagnostic testing for mitochondrial disorders.

 

This test does not assess mtDNA depletion.

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 droplet digital polymerase chain reaction (ddPCR) for confirmation and determination of heteroplasmy levels of previously detected large mitochondrial DNA (mtDNA) deletions.

 

Identification of heteroplasmy for large mtDNA deletions may assist with the diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for mtDNA deletion syndromes.

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

Large deletions in the mitochondrial genome (mtDNA deletions) cause up to 10% of primary mitochondrial disease.(1) mtDNA deletions typically present with 1 of 3 syndromes, but a large amount of clinical overlap exists. The 3 syndromes include Kearns-Sayre syndrome, Pearson syndrome, and progressive external ophthalmoplegia (PEO). Occasionally large mtDNA deletions may cause Leigh syndrome. The phenotypes for these conditions vary.

 

Kearns-Sayre syndrome typically has an age of onset of less than 20 years and is characterized by pigmentary retinopathy or PEO, cardiac conduction defects, ataxia, and an increased spinal fluid (CSF) protein level. A common, recurrent deletion spanning m.8470_13446 causes Kearns-Sayre syndrome; however, there are additional deletions that contribute to the syndrome. These deletions are detected in muscle.

 

Pearson syndrome's clinical features include sideroblastic anemia, exocrine pancreas dysfunction with symptoms in the first year of life. mtDNA deletions that cause Pearson syndrome are abundant in blood.

 

Chronic PEO can be the mildest of the mtDNA deletion phenotypes. This presentation is characterized by progressive ptosis, ophthalmoplegia, oropharyngeal, and proximal muscle weakness. mtDNA deletions that cause PEO are primarily detectable in muscle.

 

Occasionally, mtDNA deletions cause Leigh syndrome, which is characterized by psychomotor regression, abnormal brain MRI, and elevated blood and CSF lactate levels. However, other mtDNA variants may also cause Leigh syndrome. If caused by a large deletion, it is usually detectable in muscle or blood.

 

Large deletions can be present in only a fraction of mitochondria; a phenomenon known as heteroplasmy. Typically, the severity of disease presentation is a function of the degree of heteroplasmy. Determining the heteroplasmy of large mtDNA deletions is challenging by common clinical methods, such as next-generation sequencing. However, this droplet digital polymerase chain reaction method can obtain an accurate range of heteroplasmy levels in a variety of tissues.

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

The interpretation of molecular biomarker analysis includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.

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.

 

Technical Limitations:

This assay will not detect the breakpoints for large mitochondrial deletions or single nucleotide variants that cause mitochondrial disease. Therefore, the absence of a detectable variant does not rule out the possibility that an individual is affected with mitochondrial disease. This test can only detect mitochondrial DNA (mtDNA) deletions that include the mt-ND4 or mt-ND2 genes.

 

Some individuals who have a mitochondrial deletion syndrome may have a deletion that is not identified by this assay. The absence of a deletion, therefore, does not eliminate the possibility of a mitochondrial DNA deletion syndrome. For predictive testing of asymptomatic individuals, it is important to first document the presence of a deletion in an affected family member.

 

Of note, absence of a mitochondrial deletion does not rule out the presence of a deletion below the limits of detection of this assay (<10% heteroplasmy).

 

Rare variants exist that could lead to false-negative or false-positive results. If results obtained do not match clinical findings, additional testing should be considered.

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

1. Lamont PJ, Surtees R, Woodward CE, Leonard JV, Wood NW, Harding AE. Clinical and laboratory findings in referrals for mitochondrial DNA analysis. Arch Dis Child. 1998;79(1):22-27. doi:10.1136/adc.79.1.22

2. Goldstein A, Falk MJ. Mitochondrial DNA deletion syndromes. In: Adam MP, Mirzaa GM, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated May 11, 2023. Accessed June 30, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1203/

3. Legati A, Zanetti N, Nasca A, et al. Current and new next-generation sequencing approaches to study mitochondrial DNA. J Mol Diagn. 2021;23(6), 732-741

4. McCormick EM, Lott MT, Dulik MC, et al. Specifications of the ACMG/AMP standards and guidelines for mitochondrial DNA variant interpretation. Hum Mutat. 2020;41(12):2028-2057

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

This test is a droplet digital polymerase chain reaction method for determining heteroplasmy for large mitochondrial genome deletions.(Unpublished Mayo method)

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.

Monday through Friday

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.

7 to 10 days

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; Blood spots, cultured fibroblasts, skin biopsy:1 month

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 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.

81479

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
DMITO Mitochondrial Deletion Heteroplasmy 35470-4
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.
618613 Result Summary 50397-9
618614 Result 82939-0
618615 Interpretation 69047-9
618616 Additional Information 48767-8
618617 Specimen 31208-2
618618 Source 31208-2
618619 Method 85069-3
618620 Disclaimer 62364-5
618621 Released By 18771-6

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 | PHP Pdf | CMS 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