What is MELAS?

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a progressive multisystem disorder that primarily affects the nervous system and the muscles. Although rare, it is one of the most common mitochondrial diseases. The estimated prevalence of MELAS is 1-16/100,000 in the adult population[1]. Men, women, and all ethnicities are equally affected.

MELAS typically presents during childhood, although symptoms can appear as early as before age 2 or as late as after age 40 [2]. Over time, it results in neurological impairment and is often fatal. Most individuals survive ~17 years following the onset of seizures or other problems of the nervous system[3].

Medical research has not yet established a means of stopping or reversing MELAS. However, supportive treatments that can make a difference in affected individuals’ quality of life are available.

What causes MELAS?

MELAS is an inherited disorder caused by mutations that are thought to impair the assembly of mitochondria. MELAS mutations have been identified in the following mitochondrial genes:

  • MT-TL1 (mutated in an estimated 80% of MELAS cases[4])
  • MT-ND5
  • MT-TC
  • MT-TF MT-TH
  • MT-TK
  • MT-TL2
  • MT-TQ
  • MT-TV
  • MT-TW 
  • MT-TS1
  • MT-TS2
  • MT-ND1
  • MT-ND6
  • MT-CO2
  • MT-CO3
  • MT-CYB

What are the symptoms of MELAS?

The hallmark symptom of MELAS is stroke-like episodes, acute events that resemble strokes in that they involve sudden neurological symptoms such as weakness in one side of the body[2,5].

    Other common symptoms of MELAS include:

    • seizures
    • dementia
    • headaches
    • cortical vision loss
    • muscle weakness
    • vomiting
    • short stature

    MELAS is also sometimes accompanied by:

    • hearing impairment
    • learning disability
    • anxiety
    • depression
    • diabetes

      How do I know if my loved one has MELAS?

      Your loved one’s healthcare provider will determine whether he or she meets the clinical criteria for a diagnosis of MELAS. They may perform or recommend:

      • molecular genetic testing for a MELAS mutation
      • measurements of the level of lactic acid in the blood or cerebrospinal fluid (CSF)
      • blood tests for the creatine kinase enzyme
      • a muscle sample (biopsy)
      • brain-imaging such as computed tomography (CT) scan or magnetic resonance imaging (MRI)

      What are the treatments for MELAS?

      Unfortunately, there is no cure or specific treatment for MELAS. However, available treatments can help manage symptoms and improve life for individuals and their families. These treatments include:

      • arginine therapy for stroke-like episodes[6]
      • anti-epileptic medications for seizures (although Valproate should be avoided)[7]
      • vitamins such as coenzyme Q10 or L-carnitine for general benefit in some individuals
      • Moderate supervised exercise for muscle weakness
      • insulin for diabetes
      • cochlear implants for hearing loss

      Since MELAS is an inherited disorder, genetic counseling for the family may also be recommended.

        Are there any clinical trials for MELAS?

        To see if you qualify for any trials as a MELAS patient, use our Clinical Trials Finder tool at https://www.umdf.org/clinical-trials/.  We also highly encourage you to join our patient registry, mitoSHARE, where we are actively recruiting MELAS families.

          How can my family cope with MELAS?

          We are here to help. UMDF serves a number of families coping with MELAS. 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, MELAS specific support meetings, and more. They’ll also connect you with a UMDF ambassador, likely a fellow MELAS patient or family member, who can help support and guide you through your questions.

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

          • 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 MELAS 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 MELAS 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 MELAS?

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

          • Research & Funding: UMDF has provided more than $14 million in research funding to find treatments for diseases like MELAS. 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.

          I Didn’t Find What I’m Looking For Here. What Should I Do?

          UMDF Is here to help. Contact support@umdf.org to connect with our Patient Concierge.

          References

          1. Uusimaa J, Moilanen JS, Vainionpää L, et al. Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children. Ann Neurol. 2007;62(3):278-287. doi:10.1002/ana.21196
          1. El-Hattab AW, Almannai M, Scaglia F. MELAS. 2001 Feb 27 [Updated 2018 Nov 29]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1233/
          1. Kaufmann P, Engelstad K, Wei Y, et al. Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. Neurology. 2011;77(22):1965-1971. doi:10.1212/WNL.0b013e31823a0c7f
          1. Goto Y, Nonaka I, Horai S. A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990;348(6302):651-653. doi:10.1038/348651a0
          1. Lorenzoni PJ, Werneck LC, Kay CS, Silvado CE, Scola RH. When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) be the diagnosis?. Arq Neuropsiquiatr. 2015;73(11):959-967. doi:10.1590/0004-282X20150154
          1. Koga Y, Povalko N, Inoue E, et al. Therapeutic regimen of L-arginine for MELAS: 9-year, prospective, multicenter, clinical research. J Neurol. 2018;265(12):2861-2874. doi:10.1007/s00415-018-9057-7
          1. Pia S, Lui F. Melas Syndrome. [Updated 2021 Sep 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532959/