Mitochondrial disease may be
the answer you’re looking for

Did you know that mitochondrial diseases are among the most prevalent group of inherited neurological disorders?1

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.

No-cost genetic testing for
mitochondrial disease

Learn about some of the no-cost genetic testing
options available to you.

Review No-Cost Genetic Tests

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.

  • Muscles
  • Brain
  • Heart
  • Lungs
  • Liver
  • Gastrointestinal Tract
Illustration of organs in the body
body illustration highlight - musclesbody illustration highlight - muscles
body illustration highlight - brainbody illustration highlight - brain
body illustration highlight - heartbody illustration highlight - heart
body illustration highlight - lungsbody illustration highlight - lungs
body illustration highlight - liverbody illustration highlight - liver
body illustration highlight - gastrobody illustration highlight - gastro

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:

  • Muscles
  • Brain
  • Heart
  • Lungs
  • Liver
  • Gastrointestinal Tract
If multiple organ systems are involved, mitochondrial disease could be a consideration.

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.

Common symptoms of mitochondrial diseases7
Common
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 Tests
Links to learn more
United Mitochondrial Disease Foundation (UMDF)

Review mitochondrial disease information from UMDF.

Visit UMDF.org >
Mitochondrial Medicine Society (MMS)

Explore educational resources, CME opportunities, and support providers from MMS.

Visit MitoSoc.org >
Connect With a Mito Expert

Use the database of doctors within the Mitochondrial Care Network to find an expert in mitochondrial disease.

Search Database >
Mitochondrial Care Network (MCN)

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

Early onset symptoms logoEarly onset of TK2d4

Infants often have a healthy birth and reach early developmental milestones

Shortly after, they may experience rapid decline characterized by loss of motor milestones and acute respiratory insufficiency

Late onset symptoms logoLate onset of TK2d4

Facial weakness

Droopy eyelids

Difficulty eating

Shortness of breath

Proximal muscle weakness

If you suspect

tk2d magnifying glass icon

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 Tests
Links to learn more
No-cost Genetic Testing for TK2d

If you suspect that a patient may have TK2d, they may be eligible for no-cost genetic testing.

Learn More >
TakeOnTK2d

Learn more about TK2d, diagnosis, and treatment opportunities.

Visit TK2d.com >
UMDF Genetic Testing for Suspected Mitochondrial Disease

Learn more about additional genetic testing opportunities offered by UMDF.

Visit UMDF.org >
TK2d Information from MedlinePlus

Review the information on TK2d gathered and published by MedlinePlus.

Visit MedlinePlus.gov >
TK2d Information from MitoAction

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 Tests

While 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:

  1. Whole-exome sequencing/Whole-genome sequencing (NGS: Next-generation sequencing)4,11,12
  2. mtDNA Genome sequencing (NGS)11
  3. Multi-gene panel4,13
  4. 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
  1. 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
  2. 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
  3. 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
  4. 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).

mtDNA analysis11

  • Real-time polymerase chain reaction (PCR) test used to analyze mtDNA content (copy number)
  • Recommended for when an mtDNA depletion or deletion syndrome is suspected

EMG/single-fiber EMG/NCV14

  • Helps detect myopathic changes/abnormalities
  • Some patients with mitochondrial myopathy may have normal or nonspecific changes to EMG studies
  • Not specific and not a confirmatory diagnostic test

Blood and biochemical11,15

  • Can include blood lactate, pyruvate, serum creatine kinase, and many more
  • Results can raise suspicion of mitochondrial dysfunction
  • Caution must be used when interpreting these findings, as any alterations identified will not be specific to mitochondrial disease and are typically not diagnostic in isolation (warrants additional testing)

Muscle biopsy11

  • A muscle biopsy may reveal the presence of ragged red fibers, COX-deficient fibers, and mtDNA depletion or deletion
  • Previously considered the gold standard, however not always highly sensitive or specific about a particular mitochondrial disease
  • Can be painful and invasive

MRI11

  • Mitochondrial diseases produce variable imaging abnormalities in various organs, and some patterns can be very helpful in diagnosis
  • May or may not show structural alterations depending on the type of mitochondrial diseases and type of central nervous system involvement
  • Not definitive for a diagnosis

Several no-cost genetic testing programs are available to help diagnose your patients

Program Name

UMDF Genetic Testing for Suspected Mitochondrial Disease Program

Lab

Invitae

Genes Tested

Comprehensive Neuromuscular Disorders Panel
~210 genes associated with hereditary neuromuscular conditions (includes select mitochondrial nuclear genes)

Use When

You suspect that a patient may have a neuromuscular or mitochondrial disease

Eligibility

Patients from the US, Canada, Argentina, Brazil, Chile, Colombia, Mexico, and Australia (as of July 2021) suspected of having muscular dystrophy with one or more of the following:
  • • 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

  1. Physician initiates process by visiting the website and completing a paper or online order
  2. Option for US patients to initiate on the website by speaking to a third-party genetic counselor
  3. Results provided to:
    • Ordering physician
    • Patient
    • Program sponsors (aggregate de-identified patient data and physician contact information only)
  4. Genetic counseling services offered to US patients and physicians

Link

Order Neuromuscular Test >

Program Name

UMDF Genetic Testing Project

Lab

MNG Laboratories

Genes Tested

Next generation sequencing of a panel of 320 known nuclear genes associated with mitochondrial disorders as well as full mtDNA sequencing and Copy Number Analysis

Use When

You suspect that a patient may have a mitochondrial disease

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. 1. Provider downloads the Test Request Form (TRF) and orders testing kits (blood or buccal) from the MNG Laboratories website
  2. 2. TRF must be fully completed and signed by the physician and patient
  3. 3. Patient must read and sign the consent
  4. 4. Provider collects and ships the sample along with completed TRF and patient consent in the provided return box
  5. 5. Test results are provided in 4 to 6 weeks

Link

Provide Mito Test Info to Your Patient >

Program Name

No-Cost Genetic Testing Program for TK2d
Physician-initiated program

Lab

PreventionGenetics

Genes Tested

  • • TK2 single gene

  • • 55-gene panel with genes associated with limb-girdle muscular dystrophy and mitochondrial depletion syndromes, including TK2d

Use When

You suspect that a patient may have TK2d

Eligibility

US and global patients
  • • 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

  1. Physician orders testing kit
  2. Physician completes the Test Requisition Form and helps patient arrange the blood draw
  3. Results provided to:
    • Ordering physician
    • Program sponsors (aggregate de-identified patient data and physician contact information only)
  4. Genetic counseling offered to physicians

Link

Order TK2d Test >

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 Table
Program Name UMDF Genetic Testing for Suspected Mitochondrial Disease Program UMDF Genetic Testing Project Genetic Testing Program for TK2d Physician-initiated program
Lab Invitae MNG Laboratories PreventionGenetics
Genes Tested Comprehensive Neuromuscular Disorders Panel
~210 genes associated with hereditary neuromuscular conditions (includes select mitochondrial nuclear genes) 		Next generation sequencing of a panel of 320 known nuclear genes associated with mitochondrial disorders as well as full mtDNA sequencing and Copy Number Analysis
  • • TK2 single gene

  • • 55-gene panel with genes associated with limb-girdle muscular dystrophy and mitochondrial depletion syndromes, including TK2d
Use When You suspect that a patient may have a neuromuscular or mitochondrial disease You suspect that a patient may have a mitochondrial disease You suspect that a patient may have TK2d
Eligibility Patients from the US, Canada, Argentina, Brazil, Chile, Colombia, Mexico, and Australia (as of July 2021) suspected of having muscular dystrophy with one or more of the following:
  • • 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
  • • 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
 US and global patients
  • • 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
  • • Saliva or buccal swab (can be collected at home by patient)
  • • Blood (in office or at a blood draw site)
  • • Genomic DNA
  • • Buccal swab (can be collected at home by patient)
  • • Blood (in office or at a blood draw site)
  • • Blood (in office or at a blood draw site)
Process
  1. Physician initiates process by visiting the website and completing a paper or online order
  2. Option for US patients to initiate on the website by speaking to a third-party genetic counselor
  3. Results provided to:
    • Ordering physician
    • Patient
    • Program sponsors (aggregate de-identified patient data and physician contact information only)
  4. Genetic counseling services offered to US patients and physicians
  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
  1. Physician orders testing kit
  2. Physician completes the Test Requisition Form and helps patient arrange the blood draw
  3. Results provided to:
    • Ordering physician
    • Program sponsors (aggregate de-identified patient data and physician contact information only)
  4. Genetic counseling offered to physicians
Link Order Neuromuscular Test > Provide Mito Test Info to Your Patient > Order TK2d Test >

These are not the only tests available, and the list may be updated in the future.

Resources for mitochondrial diseases and TK2d

Several no-cost genetic testing programs are available to help diagnose your patients

Review No Cost Testing Table

Mitochondrial disease

Connect With a Mito Expert

Use the database of doctors within the Mitochondrial Care Network to find an expert in mitochondrial disease.

Search Database >
Mitochondrial Medicine Society (MMS)

Explore educational resources, CME opportunities, and support providers from MMS.

Visit MitoSoc.org >
Patient Care Standards for Mitochondrial Disease

Read the consensus statement from MMS.

View PDF >
Mitochondrial Care Network (MCN)

Learn about a network created to implement best practices in mitochondrial medicine.

Visit MitoNetwork.org >
United Mitochondrial Disease Foundation (UMDF)

Review mitochondrial disease information from UMDF.

Visit UMDF.org >
Diagnosis and Management of Mitochondrial Disease

Read the consensus statement from MMS.

View PDF >

Mitochondrial disease

Mitochondrial and Metabolic Medicine (M3)

Review the official journal of the MMS.

Visit MitoMedicine.com >
MitoAction Podcasts

Register for future events and review slides from previous podcasts.

Visit MitoAction.org >
Clinical Trial Information

Learn about how to participate in a clinical study or connect with a relevant research opportunity.

Visit UMDF.org >
UMDF Healthcare Provider Resources

Explore educational resources, podcasts, and more from UMDF.

Visit UMDF.org >
mitoSHARE Registry

Learn about mitoSHARE, a worldwide patient-populated registry initiative stewarded by UMDF.

Visit UMDF.org. >

TK2d

Take on TK2d

Learn more about TK2d, diagnosis, and treatment opportunities.

Visit TK2d.com >
TK2d Information from MitoAction

Explore TK2d-specific information curated by MitoAction.

Visit MitoAction.org >
TK2d Information from MedlinePlus

Review the information on TK2d gathered and published by MedlinePlus.

Visit MedlinePlus.gov >