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Test Code DMITO Mitochondrial DNA Deletion Heteroplasmy, ddPCR, 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


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 Instructions.

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 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).


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 1 of the following forms with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-Biochemical Genetics Test Request (T798)

Useful For

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.

Reflex Tests

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

Method Name

Droplet Digital Polymerase Chain Reaction (ddPCR)

Reporting Name

Mitochondrial Deletion Heteroplasmy

Specimen Type

Varies

Specimen Minimum Volume

Blood: 1 mL; Blood spots: 2 spots; Other specimen types: 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

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

An interpretive report will be provided.

Day(s) Performed

Monday through Friday

Report Available

7 to 10 days

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

81479