MERRF Syndrome

MERRF Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report MERRF Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • MERRF
  • Fukuhara syndrome
  • myoclonus epilepsy associated with ragged red fibers
  • myoencephalopathy ragged-red fiber disease

Disorder Subdivisions

  • None

General Discussion

MERRF (Myoclonus Epilepsy with Ragged-Red Fibers) syndrome is an extremely rare disorder that begins in childhood and affects the nervous system and skeletal muscle as well as other body systems. The distinguishing feature in MERRF is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. In addition, individuals with MERRF syndrome may have muscle weakness (myopathy), an impaired ability to coordinate movements (ataxia), seizures, and a slow deterioration of intellectual function (dementia). Short stature, degeneration of the optic nerve (optic atrophy), hearing loss, cardiomyopathy and abnormal sensation from nerve damage (peripheral neuropathy) are also common symptoms. Abnormal muscle cells are present and appear as ragged red fibers (RRF) when stained with the modified Gomori trichrome and viewed microscopically. MERRF is caused by mutations in mitochondrial DNA (mtDNA).

Symptoms

Symptoms of MERRF syndrome can begin in childhood, adolescence or early adulthood after a period of normal development. Symptoms and physical findings associated with MERRF syndrome vary greatly between affected individuals in the same family and between different families. Myoclonus is usually the first symptom followed by seizures, ataxia, muscle weakness and dementia. Short stature, degeneration of the optic nerve (optic atrophy), hearing loss, and altered sensation (pins-and-needles or pain) from nerve damage (peripheral neuropathy) are also common symptoms. Cardiomyopathy and the heart rhythm abnormality known as Wolff-Parkinson-White syndrome are frequently present. Occasional symptoms include benign fat cell tumors (lipomas), especially around the neck, and eye abnormalities involving melanin in the retina (pigmentary retinopathy).



People with MERRF syndrome have an accumulation of lactic acid in the blood (lactic acidosis) and often complain of vomiting, abdominal pain, fatigue, muscle weakness and difficulty breathing.

Causes

MERRF syndrome is caused by mutations in mitochondrial DNA (mtDNA).

Mutations affecting the genes of mtDNA are inherited from the mother. MtDNA in sperm cells is typically lost during fertilization and as a result, all human mtDNA comes from the mother. An affected mother will pass on the mutation to all her children, but only her daughters will pass it on to their children. Mitochondria, which are found by the hundreds or thousands in the cells of the body, carry the blueprints for regulating energy production.



Both normal and mutated mtDNA can exist in the same cell, a situation known as heteroplasmy. The number of defective mtDNAs may be out-numbered by the number of normal mtDNAs. Symptoms may not appear in any given generation until the mutation affects a significant proportion of mtDNAs. The uneven distribution of normal and mutant mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of symptoms in affected family members.



Mutations in the mtDNA gene MT-TK are associated with MERRF in approximately 90% of cases. One particular MT-TK mutation, m.8344A>G, accounts for 80% of cases. Mutations in MT-TL1, MT-TH, MT-TS1, MT-TS2 and MT-TF have also been associated with MERRF.



A few cases of MERRF syndrome appear to occur as the result of a new spontaneous mutation in a mitochondrial gene and are not inherited.

Affected Populations

MERRF syndrome is a rare disorder that affects males and females in equal numbers. Some researchers believe that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like MERRF syndrome.

Standard Therapies

Diagnosis

MERRF is diagnosed based on clinical findings and molecular genetic testing.



Clinical testing may include measurement of lactate and pyruvate concentrations in blood and CSF. CSF protein may also be elevated in MERRF syndrome. Brain imaging techniques such as magnetic resonance imaging (MRI) may be used to look for stroke-like lesions and magnetic resonance spectroscopy (MRS) is used to look for lactate in the brain. Electrocardiogram may be used to diagnose heart rhythm abnormalities. Muscle biopsy will usually show ragged red fibers.



The mtDNA mutations associated with MELAS can usually be detected in white blood cells, but due to heteroplasmy (see Causes), other tissue samples may be necessary such as skin, saliva, hair follicles, urinary sediment and skeletal muscle.



Treatment

No specific treatment is available for MERRF syndrome. Anti-convulsant drugs are used to help prevent and control seizures associated with MERRF syndrome. Levetiracetam has been effective in controlling myoclonus in a small number of patients. Therapies are sometimes used to increase energy production by the mitochondria and slow the effects of the condition. Coenzyme Q10 and L-carnitine have been beneficial in some patients.



Physical therapy and aerobic exercise may help to improve muscle weakness, stiffness and motor function.



Genetic counseling is recommended for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



Contact for additional information about MERRF syndrome:



Salvatore DiMauro, MD

Lucy G. Moses Professor of Neurology

4-424B College of Physicians & Surgeons

630 West 168th Street

New York, NY 10032

Telephone: 212-305-1662

FAX: 212-305-3986

sd12@columbia.edu

References

TEXTBOOKS.

Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2478.



Adams, RD, et al, eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:986.



Fauci AS, et al, eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:2454, 2480.



Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:2167.



Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1715.



Lyon G, et al, eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. New York, NY: McGraw-Hill Companies; 1996:256-57.



Scriver CR, et al, eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:1560-62.



Menkes JH, au, Pine JW, et al, eds. Textbook of Child Neurology, 5th ed. Baltimore, MD: Williams & Wilkins; 1995:852.



Buyse ML, ed. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific Publications; For: The Center for Birth Defects Information Services Inc; 1990:1190.



JOURNAL ARTICLES

Nissenkorn A, et al, Neurologic presentations of mitochondrial disorders. J Child Neurol. 2000;15:44-48.



Stratilova L, et al. Various manifestations of the A8344G mt DNA heteroplasmic mutation in 4 families with the MERRF syndrome. Cas Lek Cesk. 1999;138:401-05.



Fukuhara N. MERRF. Ryoikibetsu Shokogun Shirizu. 1999;27:188-90.



Chinnery PF, et al. MELAS and MERRF. The relationship between maternal mutation load and the frequency of clinically affected offspring. Brain. 1998;121:1889-94.



Noer AS, et al., A tRNA (lys) mutation in the mtDNA is the causal genetic lesion underlying myoclonic epilepsy and ragged-red fibers (MERRF) syndrome. Am J Hum Genet. 1991;49:715-22.



Palca J. The other human genome. Science. 1990;249:1104-05.



Berkovic SF, et al. Myoclonus epilepsy and ragged-red fibers (MERRF). A clinical pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study. Brain. 1989;112:1231-60.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:545000; Last Update:5/5/10.



Genetics Home Reference-U.S. Library of Medicine. http://ghr.nlm.nih.gov/condition/myoclonic-epilepsy-with-ragged-red-fibers Updated 12/09. Accessed 9/10.



DiMauro S and Hirano M. (Updated 8/18/09). MERRF. In GeneReviews at Genetests: Medical Genetics Information resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org. Accessed 9/10.

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



United Mitochondrial Disease Foundation

8085 Saltsburg Road Suite 201

Pittsburgh, PA 15239

United States

Tel: (412)793-8077

Fax: (412)793-6477

Tel: (888)317-8633

Email: info@umdf.org

Internet: http://www.umdf.org



Lactic Acidosis Support Trust

1A Whitley Close

Middlewich

Cheshire, CW10 0NQ

United Kingdom

Tel: 0160683719

Fax: 01606837198



Epilepsy Foundation

8301 Professional Place

Landover, MD 20785-7223

Tel: (866)330-2718

Fax: (877)687-4878

Tel: (800)332-1000

TDD: (800)332-2070

Email: ContactUs@efa.org

Internet: http://www.epilepsyfoundation.org



Muscular Dystrophy Association

3300 East Sunrise Drive

Tucson, AZ 85718-3208

USA

Tel: (520)529-2000

Fax: (520)529-5300

Tel: (800)572-1717

Email: mda@mdausa.org

Internet: http://www.mda.org/



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



Mitochondrial Disease Support Group Online

5022 Michigan Avenue

West Palm Beach, FL 33415

Tel: (407)641-4712

Email: madmolmom@gmail.com

Internet: http://www.mitosupport.org/



Vereniging voor Kinder met Stofwisselingsziekten

P.O. Box 664

Bloemendalstraat 11

Zwolle, 8000 AR

The Netherlands

Tel: 0384201764

Fax: 0384201447

Email: info@stofwisselingsziekten.nl

Internet: http://www.stofwisselingsziekten.nl



Children's Mitochondrial Disease Network

Mayfield House

30 Heber Walk

Chester Way

Northwich

England, CW9 5JB

United Kingdom

Tel: 440160643946

Fax: 440160643946

Email: info@cmdn.org.uk

Internet: http://www.emdn-mitonet.co.uk/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



MitoAction

14 Pembroke Street

Medford, MA 02155

Tel: (888)648-6228

Fax: (888)648-6228

Email: info@mitoaction.org

Internet: http://www.MitoAction.org



For a Complete Report

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