Mitochondrial disease may be
the answer you’re looking for
Order a genetic test early to quickly and accurately diagnose a suspected case of mitochondrial disease. Early genetic testing can give patients a path forward by confirming a diagnosis, allowing them to seek the care they need and enroll in available clinical trials.
mitochondrial disease
Learn about some of the no-cost genetic testing
options available to you.
An estimated
1 in 5,000
adults has a mitochondrial disease, the same prevalence rate as myasthenia gravis.1,6
Mitochondrial diseases are a group of rare, debilitating conditions that can severely impact daily living and quality of life and are often fatal2-4
There are many types of mitochondrial diseases, each characterized by progressively worsening symptoms and involving multiple organs or organ systems.5
While rare, mitochondrial disease may actually be more common than some may think. Several clinical trial programs are currently being conducted for different mitochondrial diseases, advancing our knowledge and providing hope for the community.








If multiple organ systems are involved, mitochondrial disease could be a consideration.
Mitochondrial diseases typically manifest as neuromuscular or metabolic conditions that most frequently impact parts of the body that require the greatest amount of energy7:
Symptoms of mitochondrial diseases vary considerably and often mimic other rare or even common diseases5
According to patient reports, patients with mitochondrial diseases experience an average of 16 symptoms.8 However, advancements in genetic testing have made them easier to diagnose despite their complex presentation.
misdiagnoses5
Reduced energy/
fatigue
Muscle weakness
Difficulty swallowing
or walking
Neurological symptoms
(e.g., epilepsy, ataxia,
hearing loss)
Fibromyalgia
Lyme disease
Chronic fatigue syndrome
Various psychiatric
disorders (e.g., conversion syndrome, depression)
Myasthenia gravis
Multiple sclerosis
According to a survey of 210 patients,
before eventually being diagnosed with a mitochondrial disease,
55%
of patients reported receiving an alternative nonmitochondrial disease diagnosis.
32%
of those patients received multiple misdiagnoses of nonmitochondrial diseases.5
Historically, the diagnostic journey has been lengthy and required many tests before a conclusion was made.5 Today, genetic testing has created a quick and direct path forward to help put an end to an often-frustrating diagnostic process.
Review No-cost Genetic TestsReview mitochondrial disease information from UMDF.
Visit UMDF.org >Explore educational resources, CME opportunities, and support providers from MMS.
Visit MitoSoc.org >Use the database of doctors within the Mitochondrial Care Network to find an expert in mitochondrial disease.
Search Database >Learn about a network created to implement best practices in mitochondrial medicine.
Visit MitoNetwork.org >Shining a light onTK2d
Thymidine kinase 2 deficiency (TK2d) is a rare, inherited, and debilitating myopathic mitochondrial disease.4
TK2d is different from other mitochondrial diseases in that it predominantly, and sometimes exclusively, manifests as myopathy (muscle disease)4
- This severe muscle weakness affects different parts of the body and often manifests as respiratory weakness, ptosis, and/or progressive external ophthalmoplegia4
- Eventually, patients may lose the ability to walk, eat, and breathe independently4
- TK2d is a deficiency of the thymidine kinase 2 enzyme, which is crucial for the maintenance and synthesis of mitochondrial DNA (mtDNA)9
- Like some other mitochondrial diseases, TK2d is a result of a defect in a nuclear gene (in this case, TK2)10
TK2d can develop at any point in a patient’s life; the earlier the onset of symptoms, the more severe they are and the quicker they progress4
If you suspect

only certain genetic tests can definitively confirm a diagnosis
The TK2 gene is found in the nuclear genome, not the mitochondrial genome.9 Whole exome sequencing, whole genome sequencing, and broad genetic panels for nuclear mitochondrial genes will usually include TK2, so they are good considerations when a TK2d diagnosis is suspected.4
Review No-Cost Genetic TestsIf you suspect that a patient may have TK2d, they may be eligible for no-cost genetic testing.
Learn More >Learn more about TK2d, diagnosis, and treatment opportunities.
Visit TK2d.com >Learn more about additional genetic testing opportunities offered by UMDF.
Visit UMDF.org >Review the information on TK2d gathered and published by MedlinePlus.
Visit MedlinePlus.gov >Explore TK2d-specific information curated by MitoAction.
Visit MitoAction.org >Discovering a path forward
Early genetic testing can confirm diagnoses, help your patients seek the care they need, and allow them to enroll in available clinical trials.
Review No-cost Genetic TestsWhile genetic testing is a fast and direct route to diagnosis, currently <40% of patients receive mitochondrial DNA (mtDNA) sequencing and <20% receive nuclear DNA (nDNA) sequencing to diagnose their mitochondrial disease.5
Most commonly ordered diagnostic tests5- Blood tests (85%)
- Muscle biopsy (71%)
- MRI (61%)
- Urine organic acids (39%)
- mtDNA (39%)
- nDNA (19%)
Patients see an average of 8 clinicians and often experience multiple misdiagnoses before their final mitochondrial disease diagnosis, but you can help shorten the diagnostic journey.5 When you suspect mitochondrial disease or TK2d, genetic testing is often the only way to definitively diagnose a patient.
Common tests for
diagnosing mitochondrial disease
-
Genetic testing4,11,12
-
mtDNA analysis11
-
EMG/single-fiber EMG/NCV14
-
Blood and biochemical11,15
-
Muscle biopsy11
-
MRI11
Genetic testing4,11,12
Due to the debilitating nature of mitochondrial disease and its myriad and complex symptom presentation, genetic testing is essential to diagnosing patients.
While whole-exome sequencing is becoming the new gold standard, a broad panel can also test for a range of diseases and may be more useful than a single-gene test that can only detect diseases affecting that specific gene.
Common genetic tests used for diagnosing mitochondrial diseases include:
- Whole-exome sequencing/Whole-genome sequencing (NGS: Next-generation sequencing)4,11,12
- mtDNA Genome sequencing (NGS)11
- Multi-gene panel4,13
- Single-gene testing11
- Becoming the new standard for diagnosing mitochondrial disease
- Widely available and becoming more affordable
- Comprehensive and capable of detecting both nuclear and mitochondrial mutations
- Not every laboratory includes both mtDNA and nDNA in their tests, so be sure to confirm with the facility when ordering the test
- Considered the gold standard for diagnosing mitochondrial diseases when mtDNA mutations are suspected
- Some mitochondrial diseases, like TK2d, are caused by mutations in the nuclear genome, which would not be revealed with this test
- A genetic testing panel inclusive of many genes associated with the disease phenotype
- Broad neuromuscular or mitochondrial panels are commonly ordered by neurologists and neuromuscular physicians
- The genes included in a multi-gene panel may vary by lab
- If you suspect TK2d or another specific disease, make sure the associated genes are on the panel
- Able to capture and diagnose a defect in the TK2 gene and other mitochondrial genes
- Very specific test that only includes a single gene—you must know which gene to test
-
Whole-exome sequencing/Whole-genome sequencing (NGS: Next-generation
sequencing)4,11,12
- Becoming the new standard for diagnosing mitochondrial disease
- Widely available and becoming more affordable
- Comprehensive and capable of detecting both nuclear and mitochondrial mutations
- Not every laboratory includes both mtDNA and nDNA in their tests, so be sure to confirm with the facility when ordering the test
-
mtDNA Genome sequencing (NGS)11
- Considered the gold standard for diagnosing mitochondrial diseases when mtDNA mutations are suspected
- Some mitochondrial diseases, like TK2d, are caused by mutations in the nuclear genome, which would not be revealed with this test
-
Multi-gene panel4,13
- A genetic testing panel inclusive of many genes associated with the disease phenotype
- Broad neuromuscular or mitochondrial panels are commonly ordered by neurologists and neuromuscular physicians
- The genes included in a multi-gene panel may vary by lab
- If you suspect TK2d or another specific disease, make sure the associated genes are on the panel
-
Single-gene testing11
- Able to capture and diagnose a defect in the TK2 gene and other mitochondrial genes
- Very specific test that only includes a single gene—you must know which gene to test
Please note that many neuromuscular genetic panels do not include nuclear and mitochondrial genes. If you are ordering a broad neuromuscular panel for genetic diagnosis of a suspected mitochondrial disease or TK2d, make sure it includes mitochondrial genes/TK2d (see below for several no-cost options).
Several no-cost genetic testing programs are available to help diagnose your patients
Program Name
Lab
Genes Tested
~210 genes associated with hereditary neuromuscular conditions (includes select mitochondrial nuclear genes)
Use When
Eligibility
- • Progressive muscle weakness
• Elevated creatine kinase levels - • Presumptive positive Duchenne muscular dystrophy from Newborn Screening Program
- • Cardiac or respiratory involvement
• Calf hypertrophy or pseudohypertrophy - • Muscle biopsy showing dystrophic changes and/or immunohistochemical evidence for specific muscular dystrophy subtype
- • Family history of muscular dystrophy
Specimen Tested
- • Saliva or buccal swab (can be collected at home by patient)
• Blood (in office or at a blood draw site)
• Genomic DNA
Process
- Physician initiates process by visiting the website and completing a paper or online order
- Option for US patients to initiate on the website by speaking to a third-party genetic counselor
- Results provided to:
• Ordering physician
• Patient
• Program sponsors (aggregate de-identified patient data and physician contact information only) - Genetic counseling services offered to US patients and physicians
Link
Program Name
Lab
Genes Tested
Use When
Eligibility
- • Ordering clinician and patient must be based in the US
• Patient must have a clinical diagnosis consistent with PMD
• Patient has never had whole-exome or whole-genome sequencing
• Patients without insurance or insurance that does not cover costs for such tests
Specimen Tested
- • Buccal swab (can be collected at home by patient)
• Blood (in office or at a blood draw site)
Process
- 1. Provider downloads the Test Request Form (TRF) and orders testing kits (blood or buccal) from the MNG Laboratories website
- 2. TRF must be fully completed and signed by the physician and patient
- 3. Patient must read and sign the consent
- 4. Provider collects and ships the sample along with completed TRF and patient consent in the provided return box
- 5. Test results are provided in 4 to 6 weeks
Link
Program Name
Physician-initiated program
Lab
Genes Tested
- • TK2 single gene
- • 55-gene panel with genes associated with limb-girdle muscular dystrophy and mitochondrial depletion syndromes, including TK2d
Use When
Eligibility
- • Patient has suspicious features of TK2
- • Patient has not had previous genetic testing for TK2d (either as single gene or as part of any previous panel testing)
- • Patient has not yet had previous testing for limb-girdle muscular dystrophy or mitochondrial depletion syndromes
- • Patient has clinical features suggestive of either limb-girdle muscular dystrophy or mitochondrial depletion syndromes
For the TK2 single gene test, the first two conditions above are required.
For the gene panel, all conditions above are required.
Specimen Tested
- • Blood (in office or at a blood draw site)
Process
- Physician orders testing kit
- Physician completes the Test Requisition Form and helps patient arrange the blood draw
- Results provided to:
• Ordering physician
• Program sponsors (aggregate de-identified patient data and physician contact information only) - Genetic counseling offered to physicians
Link
These are not the only tests available, and the list may be updated in the future.
Several no-cost genetic testing programs are available to help diagnose your patients
View No-Cost TableResources for mitochondrial diseases and TK2d
Several no-cost genetic testing programs are available to help diagnose your patients
Review No Cost Testing TableMitochondrial disease
Use the database of doctors within the Mitochondrial Care Network to find an expert in mitochondrial disease.
Search Database >Explore educational resources, CME opportunities, and support providers from MMS.
Visit MitoSoc.org >Read the consensus statement from MMS.
View PDF >Learn about a network created to implement best practices in mitochondrial medicine.
Visit MitoNetwork.org >Review mitochondrial disease information from UMDF.
Visit UMDF.org >Read the consensus statement from MMS.
View PDF >Mitochondrial disease
Review the official journal of the MMS.
Visit MitoMedicine.com >Register for future events and review slides from previous podcasts.
Visit MitoAction.org >Learn about how to participate in a clinical study or connect with a relevant research opportunity.
Visit UMDF.org >Explore educational resources, podcasts, and more from UMDF.
Visit UMDF.org >Learn about mitoSHARE, a worldwide patient-populated registry initiative stewarded by UMDF.
Visit UMDF.org. >TK2d
Learn more about TK2d, diagnosis, and treatment opportunities.
Visit TK2d.com >Explore TK2d-specific information curated by MitoAction.
Visit MitoAction.org >Review the information on TK2d gathered and published by MedlinePlus.
Visit MedlinePlus.gov >