Myoclonic Epilepsy and Ragged-Red Fiber Disease (MERRF) is a rare, multisystem mitochondrial disease hallmarked commonly by myoclonus, which is uncontrolled jerking or twitching of muscles not caused by seizures. The disease can progress to include myopathy and neurologic symptoms like epilepsy, loss of coordination (ataxia), and dementia. The clinical features of MERRF manifests after normal early development, with onset occurring from childhood to adulthood [1]. The exact prevalence is unknown, though it is estimated to be less than 1 in 100,000. The symptoms, disease progression, and prognosis vary [2].
MERRF is caused by mutations in mitochondrial DNA (mtDNA). Mitochondria, and therefore mtDNA and any associated mtDNA mutations, are passed on by the mother. Mitochondrial DNA mutations may not be present in every copy of mtDNA, meaning that some mtDNA is normal while some mtDNA is mutated. This mixture of normal and mutated mtDNA is referred to as heteroplasmy. Once a threshold of mutated mtDNA is reached in a given tissue, symptoms of mitochondrial disease occur. Levels of heteroplasmy can vary throughout the body and between affected individuals, explaining why some patients have different symptoms and disease severity. This also means that the mother may pass on the mutated gene without experiencing any symptoms herself.
The most common mutation that causes MERRF is the m.8344A>G mutation in the MT-TK gene, which is found in greater than 80% of patients with MERRF. Three less common MT-TK mutations causing MERRF include m.8356T>C, m.8363G>A, and m.8361G>A. Other causative mutations have been identified in the following genes: MT-TF, MT-TH, MT-T1, MT-Tl1, MT-TP, MT-TS1, and MT-TS2 [1].
MT-TK, the gene with the most common disease-causing mutations, encodes a transfer RNA lysine. It helps make proteins in the mitochondria, specifically adding the amino acid lysine to growing proteins. Evidence suggests that MERRF-associated mutations in MT-TK decrease protein synthesis in the mitochondria, leading to decreases in energy production [1, 3, 4]. However, it is still unclear how these defects cause the symptoms of the disease.
- Generalized epilepsy
- Loss of coordination (ataxia)
- Myopathy, including exercise intolerance, muscle weakness, and increased creatine kinase in the blood
- Ragged red fibers, a characteristic abnormality in the muscle biopsy
- Migraines
- Hearing loss
- Nerve damage outside of the brain and spinal cord called peripheral neuropathy
- Dementia
- Cardiomyopathy
- Arrythmias, such as Wolff-Parkinson-White syndrome
- Development of benign, fatty tumors called lipomatosis
- Diabetes
- Increased lactic acid in the blood called lactic acidosis
- Short stature
- Optic nerve damage called optic atrophy
- Pyramidal signs such as weakness
- Weakness or paralysis of muscles controlling the eyes called ophthalmoparesis
- Drooping upper eyelid called ptosis
Your healthcare provider can establish a diagnosis by performing molecular genetic testing for mutations in one of the genes causing MERRF in those having features of MERRF that can include one or more of the four canonical features of MERRF: myoclonus, generalized epilepsy, ataxia, and ragged red fibers in the muscle biopsy [1]. Other suggestive findings may include [1, 2]:
- Increased lactate and pyruvate in the blood and cerebrospinal fluid
- Increased cerebrospinal fluid protein concentration
- Decreased activity of respiratory chain in biochemical assay
- Slowing and discharges consistent with epilepsy on electroencephalogram (EEG), pre-excitation on electrocardiogram (ECG or EKG), and/or myopathy/neuropathy on electromyogram (EMG) and nerve conduction velocity (NCV) studies
- Loss of brain cells and connection called atrophy and other abnormalities in brain magnetic resonance imaging (MRI)
Like most forms of mitochondrial disease, there is currently no cure or specific treatment for MERRF [2]. Coenzyme Q10, l-carnitine, ubiquinol, alpha lipoic acid, vitamin E, vitamin B complex, or creatine may provide benefit to some individuals in preventing primary manifestations and preventing disease progression [1, 2]. Levetiracetam, topiramate, clonazepam, or zonisamide may be recommended for the treatment of epilepsy. Sodium valproate, carbamazepine, oxcarbazepine, and phenytoin are not recommended [2]. Mitochondrial toxins, including aminoglycoside antibiotics, linezolid, cigarettes, and alcohol, should be avoided [1, 2]. Specific symptoms should be managed by the appropriate specialists and routine surveillance is recommended [1].
We are here to help. UMDF serves a number of families coping with MERRF. 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, and more. They’ll also connect you with a UMDF ambassador, likely a fellow MERRF patient or family member, who can help support and guide you through your questions.
What are the next steps if my loved one has MERRF?
- 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 MERRF 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 MERRF 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.
- Join the conversation online
– UMDF Social Media Support Groups: Facebook Support Group
– UMDF News & Updates: Facebook | Twitter | Instagram | YouTube
- Get involved
Join the fight by giving your voice, generosity, time, or energy. Click here to see how you can help.
UMDF is helping chart a path toward treatments and eventual cure of mitochondrial diseases like MERRF through:
- Research & Funding: UMDF has provided more than $18 million in research funding to find treatments for diseases like MERRF. 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 MERRF. 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 MERRF, 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.
- For more information on MERRF, please visit:
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.
- Velez-Bartolomei et al., 2003 (last updated 2021). MERRF.
- Hameed & Tadi, 2023. Myoclonic Epilepsy and Ragged Red Fibers.