Myoclonic epilepsy with ragged red fibers

Myoclonic epilepsy with ragged red fibers (MERRF) is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. Symptoms usually first appear in childhood or adolescence after normal early development. The features of MERRF vary widely from individual to individual, even within families. Other common findings include hearing loss, short stature, optic atrophy, and cardiomyopathy with Wolff-Parkinson-White (WPW) syndrome.^[1][2] The diagnosis is based on clinical features and a muscle biopsy finding of ragged red fibers (RRF).^[1] In over 80% of cases, MERRF is caused by mutations in the mitochondrial gene called MT-TK. Several other mitochondrial genes have also been reported to cause MERRF, but many of the individuals with mutations in these other genes have additional signs and symptoms.^[2] Seizures associated with MERRF are generally treated with conventional anticonvulsant therapy.  Coenzyme Q10 and L-carnitine are often used with the hope of improving mitochondrial function.^[1]

The mitochondria are thought of as the power plant of every cell in our body (except red blood cells). They are rod-shaped or spherical structures located in our cells, and their job is to produce energy for the cell. The mitochondria have their own DNA, called mitochondrial DNA. This DNA is separate from the main DNA found in the nucleus of the cell.

If the mitochondria are not working well,  less and less energy is generated within the cell. Cell injury and even cell death can follow. If this process is repeated throughout the body, whole systems begin to fail, and the life of the person in whom this is happening is severely compromised. The onset of mitochondrial diseases is usually during childhood, but symptoms can develop in adulthood. Diseases of the mitochondria appear to cause the most damage to cells of the brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems. Depending on which cells are affected, symptoms may include loss of motor control, muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures, visual/hearing problems, lactic acidosis, developmental delays and susceptibility to infection.^[3][4]

Because muscle cells and nerve cells have especially high energy needs, muscular and neurological problems are common features of diseases that affect the mitochondria.  MERRF is a progressive multi-system syndrome with symptoms that begin during childhood, but onset may occur in adulthood. The rate of progression varies widely. Onset and extent of symptoms can differ widely from individual to individual and among affected siblings.

The classic features of MERRF include:

• Myoclonus (brief, sudden, twitching muscle spasms) – the most characteristic symptom
• Epileptic seizures
• Ataxia (impaired coordination)
• Ragged-red fibers (a characteristic microscopic abnormality observed in muscle biopsy of patients with MERRF and other mitochondrial disorders)

Additional symptoms may include: hearing loss, lactic acidosis (elevated lactic acid level in the blood), short stature, exercise intolerance, dementia, cardiac defects, eye abnormalities, and speech impairment.^[1][2]

 

While there is no cure for MERRF, there are various medications and therapies that can be helpful in managing symptoms. This includes: Antiseizure medications, levetiracetam for myoclonus, physical therapy, and aerobic exercise. Standard medication is used to treat cardiac symptoms. 

Daily use of Coenzyme Q10 and L-carnitine have been of some benefit to individuals. Other supplements that might be utilized include creatinine and lipoic acid.^[1]

Myoclonic epilepsy with ragged red fibers (MERRF) is caused by mutations in the mitochondrial DNA. Mitochondria are structures present in every cell in our body that produce usable energy from food. Although most of our DNA is located within the nucleus of our cells, mitochondria have a small amount of their own DNA known as mitochondrial or mtDNA. MtDNA contains 37 genes.^[3]

Mutations in the MT-TK gene are the most common cause of MERRF. Other genes that might be involved include but are not limited to: MT-TL1, MT-TH, and MT-TS1. Mutations within these genes reduce the ability of the mitochondria to maintain its normal function including building proteins, using oxygen, and producing energy. Organs and tissues with high energy requirements, such as the brain and muscles, are most impacted by these mutations.^[2]

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

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