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Test ID: MITOT Combined Mitochondrial Analysis, Mitochondrial Full Genome and Nuclear Gene Panel, Varies

Advisory Information


Shipping Instructions

Ambient blood is 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


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


Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 Full T-75 or 2 full T-25 flasks

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


Supplies: Fibroblast Biopsy Transport Media (T115)

Specimen Type: Skin biopsy

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. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient


Supplies: Muscle Biopsy Kit (T541)

Specimen Type: Tissue biopsy

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

Additional Information: Muscle Biopsy Shipping Kits (T541) are available.

Specimen Volume: 10-80 mg

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


Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.


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.

3. If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-Neurology Specialty Testing Client Test Request (T732)

-Inborn Errors of Metabolism Test Request (T798)

Useful For

Diagnosis of mitochondrial disease that results from mutations in either nuclear-encoded genes or the mitochondrial genome


A second-tier test for patients in whom previous targeted gene mutation analyses for specific mitochondrial disease-related genes were negative


Identification of mutations known to be associated with mitochondrial disease, allowing for predictive testing of at-risk family members

Reflex Tests

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

Testing Algorithm

If skin biopsy is received, fibroblast culture will be added and charged separately.


The following algorithms are available in Special Instructions:

-Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

-Neuromuscular Myopathy Testing Algorithm

Method Name

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

Reporting Name

Combined Mitochondrial Analysis

Specimen Type


Specimen Minimum Volume

Blood: 1 mL
Tissue Biopsy: 200 mg

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

The mitochondrion occupies a unique position in eukaryotic biology. It is the site of energy metabolism, and it is the sole subcellular organelle that is composed of proteins derived from 2 genomes, mitochondrial and nuclear. A group of hereditary disorders due to mutations in either the mitochondrial genome or nuclear mitochondrial genes have been well characterized.


The diagnosis of mitochondrial disease can be particularly challenging as the presentation can occur at any age, involve virtually any organ system, and be associated with widely varying severities. Due to the considerable overlap in the clinical phenotypes of various mitochondrial disorders, it is often difficult to distinguish these specific inherited disorders without genetic testing. This test utilizes massively parallel sequencing, also termed next-generation sequencing (NGS), to analyze 176 nuclear-encoded genes implicated in mitochondrial disease and to determine the exact sequence of the entire 16,569 base-pair mitochondrial genome.


The utility of this test is to assist in the diagnosis of mitochondrial diseases that result from mutations in both nuclear encoded genes and in the mitochondrial genome. Those diseases involving nuclear genes include disorders of mitochondrial protein synthesis, coenzyme Q10 biosynthesis, respiratory chain complexes, and mtDNA maintenance (ie, mitochondrial DNA depletion disorders). Disorders of the mitochondrial genome include those caused by point mutations, such as mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF), mitochondrial myopathy (MM), neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP), Leigh syndrome, Leber hereditary optic neuropathy (LHON), and chronic progressive external ophthalmoplegia (CPEO). In addition to the detection of single base changes with these disorders, large deletions, such as those associated with Kearns-Sayre or Pearson syndromes, are also detected. In contrast to mutations in nuclear genes, which are present in either 0, 1, or 2 copies, mitochondrial mutations can be present in any fraction of the total organelles, a phenomenon known as heteroplasmy. Typically, the severity of disease presentation is a function of the degree of heteroplasmy. Individuals with a higher fraction of mutant mitochondria present with more severe disease than those with lower percentages of mutant alleles. The sensitivity for the detection of mutant alleles in a background of wild-type (or normal) mitochondrial sequences by NGS is approximately 10%.


See Targeted Genes Interrogated by Mitochondrial Nuclear Gene Panel in Special Instructions for details regarding the targeted nuclear genes identified by this test.

Reference Values

An interpretive report will be provided.


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. For mitochondrial DNA (mtDNA) alterations, the degree of heteroplasmy of each single nucleotide or INDEL variant, defined as the ratio (percentage) of variant sequence reads to the total number of reads, will also be reported. Large mtDNA deletions will be reported as either homoplasmic or heteroplasmic, but the degree of heteroplasmy will not be estimated, due to possible preferential amplification of the smaller deletion product by long-range PCR.

Clinical Reference

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. Munnich A, Rotig A, Cormier-Daire V, Rustin P: Chapter 99: Clinical presentation of respiratory chain deficiency. In The Metabolic and Molecular Bases of Inherited Disease. Available at Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID). Edited by D Valle, AL Beaudet, B Vogelstein, et al. McGraw-Hill Medical. Retrieved 2013

3. Wallace DC, Lott MT, Brown MD, Kerstann K: Chapter 105: Mitochondria and neuro-ophthalmologic diseases. In Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID). Edited by D Valle, A Beaudet, B Vogelstein, et al. McGraw-Hill. Retrieved 2013

4. Wong LJ: Molecular genetics of mitochondrial disorders. Dev Disabil Res Rev 2010 Jun;16(2):154-162

Day(s) and Time(s) Performed

Performed weekly; Varies

Analytic Time

8 weeks

Test Classification

This test uses a standard method. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

81460-Whole Mitochondrial Genome

81440-Nuclear Encoded Mitochondrial Genes

81465 - Whole Mitochondrial Genome Large Deletion Analysis

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MITOT Combined Mitochondrial Analysis In Process


Result ID Test Result Name Result LOINC Value
48346 Result Summary 50397-9
48347 Result-mtDNA Genome Analysis 53034-5
35857 Result-Mitochondrial Nuclear Genes 40995-3
48348 Interpretation 69047-9
48349 Additional Information 48767-8
48350 Specimen 31208-2
48351 Source 31208-2
48352 Released By 18771-6
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-neurometabolic, mml-neuromuscular, mml-pediatric, mml-movement-disorders