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.

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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 it easier to diagnose despite its complex presentation.

Common symptoms of mitochondrial diseases7
Common
misdiagnoses5

Reduced energy/
fatigue

Muscle weakness

Difficulty swallowing
or walking

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

Fibromyalgia

Lyme disease

Chronic fatigue syndrome

Various psychiatric
disorders (eg, 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.

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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 an enzyme 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 the 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

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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

  • Polymerase chain reaction 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

Zogenix has sponsored several no-cost genetic testing programs to help diagnose your patients 13

Program Name

Detect Muscular Dystrophy
Physician- or patient- initiated 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)

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

Program Name

UMDF Genetic Testing Project
Patient-initiated program

Lab

Probably Genetic

Genes Tested

Whole exome sequencing covering ~20K genes including all mitochondrial nuclear genes

Use When

You suspect that a patient may have a mitochondrial disease

Eligibility

  • US patients suspected of having mitochondrial disease

    • No previous confirmed genetic diagnosis

Specimen Tested

  • • Blood (in office or at a blood draw site)

Process

  1. Patient/caregiver answers a few questions via online symptom checker and, if qualified, completes a short online intake questionnaire provided by Probably Genetic
  2. Telehealth physician completes the Test Requisition Form and orders test from GeneDx
  3. Results provided to:
    • Telehealth physician
    • Patient's physician
    • Patient/caregiver
    • Program sponsors (aggregate de-identified patient data and physician contact information only)
  4. Genetic counseling offered to patients post-test by Probably Genetic

Link

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

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

Zogenix has sponsored several no-cost genetic testing programs to help diagnose your patients13

View No-Cost Table

Resources for mitochondrial diseases and TK2d

Zogenix has sponsored several no-cost genetic testing programs to help diagnose your patients.13

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 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 >

TK2d

Take on TK2d

Learn more about TK2d, diagnosis, and treatment opportunities.

Visit TK2d.com >
NeuroSeriesLive Speaker Presentation on TK2d

Three mito experts give a CME presentation on progressive myopathy, mitochondrial disease, and TK2d. Login required, previously recorded.

Visit NeuroSeriesLive.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 >