MEPAN

Mitochondrial Disease Types

What is MEPAN?

Mitochondrial Enoyl CoA Reductase Protein-Associated Neurodegeneration (MEPAN) is a rare mitochondrial disease that affects the brain and the nerves. It was first described in the medical literature in 2016 as the first disorder to be linked to defects in the mitochondrial fatty acid synthesis pathway[1]. Three of the five affected families in this study were of Ashkenazi Jewish descent[1], suggesting that MEPAN is more prevalent in this population.

The characteristics and course of MEPAN are still under investigation. Thus far, it is thought that the disease appears as movement disorder in early childhood, which may include dystonia and/or ataxia (ages 1-6.5 years)[2]. Brain MRI may be abnormal and consistent with Leigh syndrome. MEPAN gets worse over time, and affected individuals may need assistance with movement and speech. Individuals also begin to experience reduced vision between 4 and 12 years of age; this vision loss may eventually leave them without functional sight in adulthood[2]. In contrast to some other mitochondrial disorders, however, intellectual ability is often, but not always, preserved[1].

Treatments for MEPAN focus on symptom management and may help individuals maintain mobility and skills as well as improve their quality of life[2]. In addition, some mitochondrial supplements may be effective, including C8 (octanoic acid) and alpha lipoic acid.

What causes MEPAN?

MEPAN is caused by inherited mutations in MECR, a mitochondrial gene that encodes an enzyme in the mitochondrial fatty acid synthesis pathway called mitochondrial trans-2-enoyl-coenzyme A-reductase[1]. The mitochondrial fatty acid synthesis pathway produces fatty acids and profoundly impacts energy generation in the cell[3].

 

What are the symptoms of MEPAN?

The first sign of MEPAN to appear is movement disorder and affected individuals may experience[2]:

  • uncontrolled/jerky movements
  • problems with balance
  • speech problems

Vision loss is also a symptom of MEPAN. However, this symptom typically does not appear until several years after the onset of movement disorder[2].

 

How do I know if my loved one has MEPAN?

If your loved one has symptoms of MEPAN, their healthcare provider may perform the following to establish a diagnosis[2]:

  • molecular genetic testing for mutations that causes MEPAN (through whole exome or whole genome sequencing)
  • brain-imaging such as magnetic resonance imaging (MRI)

What are the treatments for MEPAN?

Options for addressing the symptoms of MEPAN include[2]:

  • Drugs such as anticholinergic agents, baclofen, and benzodiazepines for involuntary muscle movements
  • Physical and occupational therapy to maintain or increase mobility
  • Braces, walkers, and wheelchairs for mobility
  • Speech therapy and/or augmentative communication devices for speech issues
  • Visual aids for vision loss
  • Dietary supplements are under investigation, including C8 (octanoic acid) and alpha lipoic acid.
  • Genetic counseling may also be recommended for families since MEPAN is an inherited disorder.

Are there any clinical trials for MEPAN?

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 MEPAN families.

How can my family cope with MEPAN?

We are here to help. 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 MEPAN patient or family member, who can help support and guide you through your questions.

What are the next steps if my loved one has MEPAN?

  • Get Support
    Connect with our Support & Education Team online, via email at support@umdf.org or phone at (888) 900-6486.
  • Join our patient registry, mitoSHARE
    We are actively recruiting MEPAN 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 MEPAN 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 where you – and your friends and family – can let Congress know we need their support. Click here to sign up.

What is UMDF doing about MEPAN?

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

  • Research & Funding: UMDF has provided more than $14 million in research funding to find treatments for diseases like MEPAN. 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 MEPAN. Attendance at our support meetings annually tops 7,000, including disease specific support meetings for families.
  • Clinician Support: To help educate clinicians on diseases like MEPAN, we feature monthly Bench to Bedside clinician 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 MEPAN?

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. Heimer G, Kerätär JM, Riley LG, et al. MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder. Am J Hum Genet. 2016;99(6):1229-1244. doi:10.1016/j.ajhg.2016.09.021
  1. Heimer G, Gregory A, Hogarth P, et al. MECR-Related Neurologic Disorder. 2019 May 9. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540959/
  1. Nowinski SM, Solmonson A, Rusin SF, et al. Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria. Elife. 2020;9:e58041. Published 2020 Aug 17. doi:10.7554/eLife.58041