MERRF+Syndrome

Myoclonic Epilepsy with Ragged Red Fibers (MERRF)
 * Name**

MERRF is a mitochondrial disease caused by a point mutation in a mitochondrial gene. This mutation could be in one of several genes, but over 80% of the time, it is found in the MT-TK gene. The mutation is maternally inherited and it disrupts oxidative phosphorylation, the process that uses energy to reform ATP. The MT-TK gene is involved in the creation of transfer RNAs that carry lysine. Because this tRNA is disrupted from the mutation, certain proteins that are essential for oxidative phosphorylation are not created correctly, which is why the process is so severely affected.
 * Root Cause**

MERRF affects muscle cells (mostly skeletal) and nerve cells. Affected mitochondria can accumulate in these cells and appear as red fibers when stained. Muscular twitches, stiffness, and weakness are all common. The nervous system is strongly affected, as seizures occur often and hearing and vision are impaired. Difficulty coordinating movement and dementia show that the brain is also affected over time. Also over time, the circulatory system is damaged, as cardiac muscle tissue is sometimes affected, leading to heart diseases.
 * Affected cells/tissues/organs/systems**

MERRF symptoms were known as a specific disease for some time, but there appears be a good amount of research in the early 90’s that actually pegged the cause of the symptoms to a mutation in mtDNA. It seems to have a group of collective discovers. Some of these articles can be found in the reference section below. It seems to be a relatively newly understood disease, and even today there is still much to learn. It is such an uncommon disease that there are not really any historical events linked to it. Researchers suspect that many people live with mitochondrial diseases and never report anything about it, making the number of occurrences even lower.
 * Historical background**

Symptoms of MERRF usually appear during childhood. These include the already mentioned muscular twitches and weakness, as well as seizures and hearing and vision difficulties. A low pH in body tissues and blood can lead to build up of lactate. Short stature and the inability to deal with physical activity are also common symptoms. Over time, the heart and normal cognitive function may both be impaired. Muscle cells will show high conglomerates of diseased mitochondrion.
 * Symptoms**

There is no cure for MERRF, as improving mitochondrial function is very difficult. Coenzyme Q10 has been studied as a treatment, but not very successfully. Treatments are given to help individual symptoms.
 * Treatments**

The older research done on MERRF dealt with the association of MERRF symptoms with mutations in certain genes in mtDNA (Seibel et al. 1990). One of these older papers studied the nature of the mitochondrial mutation, showing that it is also present in people of all different ages of who are not affected by MERRF (Miinscher et al. 1993). This likely had important important implications in future research on the disease. More recently, research has been done on Coenzyme Q10 and how high concentrations of it can improve mitochondria functionality. This is a new thread of research and isn't backed up by enough evidence to be considered very significant yet (De la Mata et al. 2012). A 2014 research paper discussed treatment of mitochondrial diseases like MERRF through microinjection into the embryo. By altering things early on using this method known as mitochondrial transfer, the disease may be able to be cured in the future (Liu et al. 2014).
 * Research**


 * References:**

(2014, May 1st). Myoclonic Epilepsy with Ragged Red Fibers. Genetics Home Reference. Retrieved October 10th, 2014 from: http://ghr.nlm.nih.gov/ condition/myoclonic-epilepsy-with-ragged-red-fibers

Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. & Water. P. (2007). Molecular Biology of the Cell. New York, NY. Garland Science.

De la Mata, M., Garrido-Maraver, J., Cotán, D., Cordero, M. D., Oropesa-Ávila, M., Izquierdo, L. G., ... & Sánchez-Alcázar, J. A. (2012). Recovery of MERRF fibroblasts and cybrids pathophysiology by coenzyme Q10. Neurotherapeutics, 9(2), 446-463.

Liu, C. S., Chang, J. C., Kuo, S. J., Liu, K. H., Lin, T. T., Cheng, W. L., & Chuang, S. F. (2014). Delivering healthy mitochondria for the therapy of mitochondrial diseases and beyond. The international journal of biochemistry & cell biology, 53, 141-146.

Münscher, C., Rieger, T., Müller-Höcker, J., & Kadenbach, B. (1993). The point mutation of mitochondrial DNA characteristic for MERRF disease is found also in healthy people of different ages. FEBS letters, 317(1), 27-30.

Seibel, P., Degoul, F., Romero, N., Marsac, C., & Kadenbach, B. (1990). Identification of point mutations by mispairing PCR as exemplified in MERRF disease. Biochemical and biophysical research communications, 173(2), 561-565.

Yasukawa, T., Suzuki, T., Ishii, N., Ohta, S., & Watanabe, K. (2001). Wobble modification defect in tRNA disturbs codon–anticodon interaction in a mitochondrial disease. The EMBO journal, 20(17), 4794-4802.