Mitochondrial disease may be
the answer you’re looking for

Did you know that ~1 in 5,000 adults has a mitochondrial disease? They 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.2-5

Connect with a mito expert to learn more.

There are genetic testing
options available at no cost
for mitochondrial diseases

Review No-Cost Genetic Tests

An estimated

1 in 5,000

adults has a mitochondrial disease, the same prevalence rate as myasthenia gravis.1,9

Mitochondrial diseases are a group of rare, debilitating, and often fatal conditions with severe impacts on daily living and quality of life2,6-7

There are many types of mitochondrial diseases, each characterized by progressively worsening symptoms and involving multiple organs or organ systems.8 While rare, mitochondrial disease may actually be more common than some may think.1,2,9

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 - muscles
body illustration highlight - muscles

Related symptoms10:

Myopathy, dysphagia, respiratory weakness, ptosis, ophthalmoplegia, fatigue

body illustration highlight - brain
body illustration highlight - brain

Related symptoms10:

Intellectual/developmental disability, neuroregression, epilepsy, headaches, neuropathy

body illustration highlight - heart
body illustration highlight - heart

Related symptoms10:

Cardiomyopathy, arrhythmias, cardiac anomalies (eg, left ventricular ejection fraction, left ventricular hypertrophy, late gadolinium enhancement)

body illustration highlight - lungs
body illustration highlight - lungs

Related symptoms10:

Respiratory insufficiency, respiratory infections, abnormal breathing, cough, sleep disturbances, exercise intolerance

body illustration highlight - liver
body illustration highlight - liver

Related symptoms10:

Liver dysfunction, liver disease, liver failure

body illustration highlight - gastro
body illustration highlight - gastro

Related symptoms10:

Intestinal dysmotility, constipation, poor weight gain, obesity, difficulty swallowing

If multiple organ systems are impacted, it could be a mitochondrial disease. Genetic testing can confirm diagnosis.

Mitochondrial diseases typically manifest as neuromuscular or metabolic conditions. They often impact parts of the body that require the most energy10:

  • Muscles
  • Brain
  • Heart
  • Lungs
  • Liver
  • Gastrointestinal tract

If multiple organ systems are impacted, it could be a mitochondrial disease. Genetic testing can confirm diagnosis.

Symptoms of mitochondrial diseases vary considerably and often mimic other diseases8

Patients with mitochondrial diseases report an average of 16 symptoms.11

The complex presentation is a barrier to diagnosis, often resulting in misdiagnoses or no diagnosis at all. However, advancements in genetic testing have made diagnosing mitochondrial diseases easier. If you see red-flag symptoms of mitochondrial diseases, order genetic testing right away.

Red-flag symptoms of mitochondrial diseases4,10,12,13
Common
misdiagnoses8

Red-flag symptoms of mitochondrial diseases4,10,12,13

Reduced energy/
fatigue

Muscle weakness

Difficulty swallowing
or walking

Neurological symptoms
(eg, epilepsy, ataxia,
hearing loss)

In infants: hypotonia,
weakness, failure to thrive,
and metabolic acidosis
(especially lactic acidosis)

Common
misdiagnoses8

Fibromyalgia

Lyme disease

Chronic fatigue syndrome

Various psychiatric
disorders (eg, conversion syndrome, depression)

Myasthenia gravis

Multiple sclerosis

Delayed and incorrect diagnoses are common for patients with mitochondrial diseases

55%

of patients reported receiving an incorrect nonmitochondrial disease diagnosis.

32%

of those patients received multiple misdiagnoses of nonmitochondrial diseases.8

Historically, the diagnostic journey has been lengthy and required many tests before a conclusion was made.8 Now, genetic testing provides the most direct path to diagnosis, as long as the test is inclusive of genes involved in mitochondrial function.3,4 If prior tests did not include genes involved in mitochondrial function, then it’s important to order the right genetic test and try again with patients who may have a mitochondrial disease.

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Shining a light onTK2d

Shining a light on

TK2d

Thymidine kinase 2 deficiency (TK2d) is a rare, inherited, debilitating, and often fatal myopathic mitochondrial disease.2,3 It is also a mitochondrial depletion syndrome (MDS), a category of mitochondrial disease.14

TK2d is a primary mitochondrial myopathy that is different from other mitochondrial diseases in that it predominantly, and sometimes exclusively, manifests as myopathy (muscle disease)2

  • This severe muscle weakness affects different parts of the body and often manifests as respiratory weakness, ptosis, and/or progressive external ophthalmoplegia2
  • Patients may lose the ability to walk, eat, and breathe independently2,4
  • TK2d is often fatal, with a median post-onset survival expectancy of at least 13 years for patients with early-onset disease2
  • TK2d is a deficiency of the thymidine kinase 2 enzyme, which is crucial for the maintenance and synthesis of mitochondrial DNA (mtDNA)15
  • Like some other mitochondrial diseases, TK2d is a result of a defect in a nuclear gene (in this case, TK2)16

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 progress.2 Ask your patients about their age of symptom onset in order to collect a full clinical history.

Patients with TK2d may be diagnosed years after symptom onset. Even those diagnosed as adults may have early-onset TK2d if their symptoms began at or before 12 years old.

Early onset symptoms logoEarly onset of TK2d2,3,13

Onset from 0-12 years

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.

The median post-onset survival for early-onset TK2d is at least 13 years. Patients with symptom onset before age 1 have a median post-onset survival of only 1 year.

Late onset symptoms logoLate onset of TK2d2,4

Onset after age 12

Symptoms do not progress as quickly as early onset of TK2d, but they still have a negative impact on life expectancy and quality of life.

They include facial weakness, droopy eyelids, difficulty eating, shortness of breath, and proximal muscle weakness.

If you suspect

tk2d magnifying glass icon

only certain
genetic tests
can definitively confirm a diagnosis

That means some patients may need further genetic testing.

The TK2 gene is found in the nuclear genome, not the mitochondrial genome.15 Whole-exome sequencing, whole-genome sequencing, and broad genetic panels for nuclear mitochondrial genes usually include TK2. Consider them when you suspect a patient has TK2d.2

Because of the progressive nature of TK2d, early diagnosis is crucial. Delays in diagnosis and subsequent treatment may lead to fatalities and morbidities.

Explore No-cost Genetic Tests

Discovering a path forward

Utilize genetic testing early to 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.3-5,8

Other diagnostic tests are ordered much more frequently8:

  • Blood tests (85%)
  • Muscle biopsy (71%)
  • MRI (61%)
  • Urine organic acids (39%)

Patients with mitochondrial diseases see an average of 8 clinicians and often receive multiple misdiagnoses before getting the right one.8

You can help shorten the diagnostic journey. When you suspect a mitochondrial disease like TK2d, order genetic testing to definitively diagnose a patient.

Common tests for
diagnosing mitochondrial disease

  • Genetic testing2,17-20

  • mtDNA analysis17

  • EMG/single-fiber EMG/NCV21

  • Blood and biochemical12,17

  • Muscle biopsy17

  • MRI17

Genetic testing2,17-20

Genetic testing is essential for the definitive diagnosis of mitochondrial diseases.

Many neuromuscular genetic panels do not include nuclear or mitochondrial genes. If you suspect a mitochondrial disease and order a broad neuromuscular panel, ensure it includes mitochondrial genes and TK2d.

If you ordered genetic tests for patients in the past that did not include these genes and results were negative, you may need to reanalyze the original sample or re-test.

4 common genetic tests used for diagnosing mitochondrial diseases are:

  1. Whole-exome sequencing/whole-genome sequencing (NGS: Next-generation sequencing)2,17-19
  2. mtDNA genome sequencing (NGS)17
  3. Multi-gene panel (NGS)2,20
  4. Single-gene testing17
  • Becoming the standard for diagnosing mitochondrial disease in combination with mtDNA genome sequencing
  • 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
  • Should be utilized 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
  • 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

Genetic testing is essential for the definitive diagnosis of mitochondrial diseases.

Many neuromuscular genetic panels do not include nuclear or mitochondrial genes. If you suspect a mitochondrial disease and order a broad neuromuscular panel, ensure it includes mitochondrial genes and TK2d.

If you ordered genetic tests for patients in the past that did not include these genes and results were negative, you may need to reanalyze the original sample or re-test.

4 common genetic tests used for diagnosing mitochondrial diseases are:

  1. Whole-exome sequencing/whole-genome sequencing (NGS: Next-generation sequencing)2,17-19
    • Becoming the standard for diagnosing mitochondrial disease in combination with mtDNA genome sequencing
    • 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)17
    • Should be utilized 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 panel (NGS)2,20
    • A genetic testing panel inclusive of many genes associated with the disease phenotype
    • 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 testing17
    • 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

mtDNA analysis17

  • Real-time polymerase chain reaction (PCR) test used to analyze mtDNA content (copy number)
  • Recommended for when an mtDNA depletion or deletion syndrome, such as TK2d, is suspected
  • Genetic testing inclusive of mitochondrial genes, including TK2, is the most direct path to diagnosis.

EMG/single-fiber EMG/NCV21

  • Helps detect myopathic changes/abnormalities
  • Some patients with a mitochondrial myopathy, such as TK2d, may have normal or nonspecific changes to EMG studies
  • Not specific and not a confirmatory diagnostic test
  • Genetic testing inclusive of mitochondrial genes, including TK2, is the most direct path to diagnosis.

Blood and biochemical12,17

  • Can include blood lactate, pyruvate, serum creatine kinase, and many more
  • Requires caution when interpreting findings, as any alterations identified will not be specific to a mitochondrial disease, such as TK2d. Findings are not typically diagnostic and warrant additional testing
  • Results can raise suspicion of mitochondrial dysfunction
  • Genetic testing inclusive of mitochondrial genes, including TK2, is the most direct path to diagnosis.

Muscle biopsy17

  • A muscle biopsy may reveal the presence of ragged red fibers, COX-deficient fibers, and mtDNA depletion or deletion
  • Can be painful and invasive
  • Previously considered the gold standard, but is not always highly sensitive or specific about a particular mitochondrial disease, such as TK2d
  • Genetic testing inclusive of mitochondrial genes, including TK2, is the most direct path to diagnosis.

MRI17

  • Mitochondrial diseases, such as TK2d, 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
  • Genetic testing inclusive of mitochondrial genes, including TK2, is the most direct path to diagnosis.

Several no-cost genetic tests are available for mitochondrial diseases20

The TK2 gene is not on all of the commonly used genetic testing panels for diseases that mimic TK2d, so if TK2d is part of the differential diagnosis, it is important to confirm gene coverage before ordering a panel.2-4,15

Several no-charge genetic testing options available in the US that include the TK2 gene*:

Detect Muscular Dystrophy (Invitae)22

Initiated by:
Patient or provider

Sample Source:
Saliva/buccal swab or blood

Test:
Gene panel

Behind the Seizure (Invitae)23-24

Initiated by:
Provider

Sample Source:
Saliva/buccal swab or blood

Test:
Gene panel

UMDF Genetic Testing Project (MNG Labs)25-26

Initiated by:
Provider

Sample Source:
Blood or buccal

Test:
Gene panel, mtDNA, and CNA

No-Cost Genetic Testing Program for Thymidine Kinase 2 Deficiency (Prevention Genetics)27

Initiated by:
Provider

Sample Source:
Blood

Test:
Single gene or gene panel

Probably Genetic28-30

Initiated by:
Patient

Sample Source:
Saliva/buccal swab

Test:
WES, including mtDNA

*This is not an exhaustive list of no-cost genetic testing options for TK2d.

Several no-cost genetic tests are available for mitochondrial diseases20

The TK2 gene is not on all of the commonly used genetic testing panels for diseases that mimic TK2d, so if TK2d is part of the differential diagnosis, it is important to confirm gene coverage before ordering a panel.2-4,15

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Resources for mitochondrial diseases and TK2d

There are several resources for you and your patients when it comes to diagnosing mitochondrial disease.20

Explore Resources

Mitochondrial disease resources and support for providers and patients

Connect With a Mito Expert

Use this database 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 >
Mitochondrial and Metabolic Medicine (M3)

Review the official journal of the MMS.

Visit MitoMedicine.com >
Mitochondrial Medicine Society (MMS)

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

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

Review mitochondrial disease information from UMDF.

Visit UMDF.org >
MitoAction Podcasts

Register for future events and review slides from previous podcasts.

Visit MitoAction.org >
Patient Care Standards for Mitochondrial Disease

Read the consensus statement from MMS.

View PDF >
Diagnosis and Management of Mitochondrial Disease

Read the consensus statement from MMS.

View PDF >
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 >
Connect With a Mito Expert

Use this database to find an expert in mitochondrial disease.

Search Database >
Mitochondrial and Metabolic Medicine (M3)

Review the official journal of the MMS.

Visit MitoMedicine.com >
United Mitochondrial Disease Foundation (UMDF)

Review mitochondrial disease information from UMDF.

Visit UMDF.org >
Mitochondrial Care Network (MCN)

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

Visit MitoNetwork.org >
Mitochondrial Medicine Society (MMS)

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

Visit MitoSoc.org >
MitoAction Podcasts

Register for future events and review slides from previous podcasts.

Visit MitoAction.org >

Mitochondrial disease resources and support for providers and patients

Patient Care Standards for Mitochondrial Disease

Read the consensus statement from MMS.

View PDF >
Clinical Trial Information

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

Visit UMDF.org >
mitoSHARE Registry

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

Visit UMDF.org. >
Diagnosis and Management of Mitochondrial Disease

Read the consensus statement from MMS.

View PDF >
UMDF Healthcare Provider Resources

Explore educational resources, podcasts, and more from UMDF.

Visit UMDF.org >

TK2d resources and support for providers and patients

Take on TK2d

Learn more about TK2d and diagnosis.

Visit TK2d.com >
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 >
Muscular Dystrophy Association (MDA)

Explore resources from the MDA, which supports people living with neuromuscular diseases, such as mitochondrial DNA depletion syndromes (MDS) like TK2d.

Visit MDA.org >
TK2d Information from United Mitochondrial Disease Foundation (UMDF)

Explore information about TK2d from the UMDF.

Visit UMDF.org >
Take on TK2d

Learn more about TK2d and diagnosis.

Visit TK2d.com >
TK2d Information from MitoAction

Explore TK2d-specific information curated by MitoAction.

Visit MitoAction.org >
TK2d Information from United Mitochondrial Disease Foundation (UMDF)

Explore information about TK2d from the UMDF.

Visit UMDF.org >
TK2d Information from MedlinePlus

Review the information on TK2d gathered and published by MedlinePlus.

Visit MedlinePlus.gov >
Muscular Dystrophy Association (MDA)

Explore resources from the MDA, which supports people living with neuromuscular diseases, such as mitochondrial DNA depletion syndromes (MDS) like TK2d.

Visit MDA.org >