Primary Mitochondrial Myopathies

What are primary mitochondrial myopathies?

Primary mitochondrial myopathies (PMM) are a group of genetically defined mitochondrial diseases that principally affect the muscle[1]. These disorders can affect males, females, and individuals from any ethnic or racial group. Their prevalence is currently unknown. 

PMM may present at any age. In general, more severe forms of the disease appear earlier in life. Prognosis depends on the causative gene and the age of onset.

There is no cure for PMM. However, treatments can improve or slow the progression of specific symptoms.

What causes primary mitochondrial myopathies?

PMM is caused by inherited gene mutations in mitochondrial or nuclear DNA. More than 350 genes have been linked to PMM[2]. Mutations in these genes lead to defects in normal mitochondrial function which is responsible for the metabolic process that controls the majority of energy generation in the cell. 

What are the symptoms of primary mitochondrial myopathies?

Chronic Progressive External Ophthalmoplegia (CPEO) is the most common feature of PMM[1]. Its symptoms include:

  • drooping eyelids (ptosis)
  • paralysis of the muscles that control eye movement
  • and in some cases, weakness of the limbs
Other symptoms of PMM include[1,3]:

  • exercise intolerance
  • fatigue
  • and in severe forms; difficulty swallowing (dysphagia)
  • slow or slurred speech (dysarthria)
  • muscle wasting
  • shortness of breath

Early onset forms of PMM may also include[1]

  • diminished muscle tone (hypotonia)
  • failure to thrive
  • breathing difficulty
  • reduced or absent tendon reflexes

How do I know if my loved one has a primary mitochondrial myopathy?

A diagnosis of PMM is based on the presence of PMM symptoms and a confirmation by the results of specific specialized tests. To determine if your loved one has PMM, his or her healthcare provider may perform or recommend [3]:

  • molecular genetic testing for PMM genes
  • exercise testing to test muscle function
  • measurements of the level of lactic acid in the blood or cerebrospinal fluid (CSF)
  • blood tests for metabolic enzymes and/or activity
  • electrical tests of muscle and nerve activity (electromyography and nerve conduction studies)
  • a muscle sample (biopsy)
  • brain-imaging such as computed tomography (CT) scan or magnetic resonance imaging (MRI)

What are the treatments for primary mitochondrial myopathies?

There is no specific treatment for PMM at this time. There are however treatments that can address PMM symptoms and improve quality of life which include [3,4]

  • exercise and physical therapy for skeletal muscle problems
  • proper nutrition and hydration for the body
  • a combination of vitamins and supplements “cocktail” to improve muscle function and general health
  • ophthalmological services for symptoms of the eye
  • speech therapy for speech difficulties
  • For a specific PMM caused by mutations in a gene called TK2, nucleoside therapy might be beneficial and should be discussed with your provider as specific clinical trials might be available

Genetic counseling for the family may also be recommended since PMM is inherited and the pattern of inheritance varies depending on the causative gene.

Are there any clinical trials for primary mitochondrial myopathy?

To see what trials you may qualify for, visit our Clinical Trials page – which also includes a Clinical Trials Finder Tool. We also highly encourage you to join our patient registry, mitoSHARE, where we are actively recruiting primary mitochondrial myopathies families.

How can my family cope with a primary mitochondrial myopathy?

We are here to help. UMDF serves a number of families coping with PMM. We suggest you reach out to our Support & Education Team – online, via email at support@umdf.org or phone at (888) 900-6486 – who can suggest a host of resources including doctors, disease specific support meetings, and more. They’ll also connect you with a UMDF ambassador, likely a fellow PMM patient or family member, who can help support and guide you through your questions.

What are the next steps if my loved one has a primary mitochondrial myopathy?

  • Get Support
    Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.
  • Check our Clinical Trials Finder
    Use our Clinical Trials Finder to see if you qualify for any clinical trials.
  • Join our patient registry, mitoSHARE
    We are actively recruiting PMM families to participate in our patient registry, mitoSHARE. Patient registries like mitoSHARE are an integral part in charting a course toward treatments and cures for PMM and other mitochondrial diseases. There are currently over 30 active mitochondrial disease clinical trials. Next generation patient registries like mitoSHARE are an integral part of expanding that number.
  • Become an advocate
    Ask your representatives to prioritize mitochondrial disease research and support via the UMDF Advocacy Center. We’ll send regular action items so you – and your friends and family – can let Congress know where we need their support. Click here to sign up.

What is UMDF doing about primary mitochondrial myopathies?

UMDF is helping chart a path toward treatments and eventual cure of mitochondrial diseases like PMM through:

  • Research & Funding: UMDF has provided more than $14 million in research funding to find treatments for diseases like primary mitochondrial myopathies. UMDF advocacy has helped secure an additional $55 million in federal funding via the Department of Defense and National Institutes of Health.
  • Data: Over two decades ago, UMDF pioneered patient registries for the mitochondrial disease community. Today, our next generation patient registry, mitoSHARE, is helping chart a path toward the treatment and eventual cure of mitochondrial diseases.
  • Patient Support: Thousands of families just like you depend upon UMDF for support and education on diseases like PMM. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for families.
  • Clinician Support: To help educate clinicians on primary mitochondrial myopathies and other mitochondrial diseases, we feature monthly Bench to Bedsideclinician seminars, host the annual Mitochondrial Medicine Symposium, support the Mitochondrial Care Network, and educate clinicians on our Mito U platform.

    Where can I find more information on primary mitochondrial myopathies?

    I didn’t find what I’m looking for here. What should I do?

    UMDF is here to help. Contact the Support Line at (888) 900-6486 weekdays from 8:00am to 5:00pm EST to connect with our Patient Concierge. Or, via email contact support@umdf.org.

    References

    1. Mancuso M, McFarland R, Klopstock T, Hirano M; consortium on Trial Readiness in Mitochondrial Myopathies. International Workshop:: Outcome measures and clinical trial readiness in primary mitochondrial myopathies in children and adults. Consensus recommendations. 16-18 November 2016, Rome, Italy. Neuromuscul Disord. 2017;27(12):1126-1137. doi:10.1016/j.nmd.2017.08.006
    1. Arena IG, Pugliese A, Volta S, Toscano A, Musumeci O. Molecular Genetics Overview of Primary Mitochondrial Myopathies. J Clin Med. 2022;11(3):632. Published 2022 Jan 26. doi:10.3390/jcm11030632
    1. de Barcelos IP, Emmanuele V, Hirano M. Advances in primary mitochondrial myopathies. Curr Opin Neurol. 2019;32(5):715-721. doi:10.1097/WCO.0000000000000743
    1. Parikh S, Goldstein A, Karaa A, et al. Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society. Genet Med. 2017;19(12):10.1038/gim.2017.107. doi:10.1038/gim.2017.107