Myoclonus epilepsy with ragged-red fiber (MERRF) patients present with symptoms related to the central and peripheral nervous system, ocular and cardiovascular apparatus and subcutaneous tissues. The main trait of this disease is myoclonus, consisting of involuntary, brief, sudden spasms affecting extremities. Other peripheral nervous system involvement signs include muscle weakness, as an expression of myopathy, progressive muscular spasticity, peripheral neuropathy, optic nerve atrophy or progressive external ophthalmoplegia and hearing loss. Central nervous system involvement causes seizures, ataxia, depression [1] and dementia, as well as the presence of pyramidal signs on evaluation.

The cardiovascular system is involved with patients developing a form of dilative cardiomyopathy after a period of normal development [2]. Affected individuals also have heart rhythm abnormalities, a type of preexcitation syndrome known as Wolff-Parkinson-White syndrome, premature ventricular contractions, incomplete left bundle branch block and other, unrelated findings such as a short stature, lipomas, abdominal pain, recurrent vomiting, fatigue, exercise intolerance, dyspnea (caused by lactic acid accumulation) and pigmentary retinopathy. Cardiac involvement may progress to subclinical left ventricular dysfunction or overt heart failure. Cases of stroke [3] [4] or stroke-like episodes [5] have also been described. This condition may also be associated with other diseases, such as atypical Charcot-Marie-Tooth and Leigh syndrome, diabetes mellitus and migraine headaches [6].

Other unusual manifestations include spasmodic dysphonia [7], acute demyelinating disease [8] and sudden infant death syndrome [9].

• Epilepsy

  (MERRF syndrome) myoclonic epilepsy with ragged red fibers Fukuhara syndrome Myoclonus with epilepsy and with Ragged Red Fibers Myoclonic epilepsy - ragged red fibers Myoclonus epilepsy AND ragged red fibers MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED-RED [wikidata.org]

  There are no guidelines available for the management of epilepsy in MERRF syndrome but several expert opinions and general recommendations for the treatment of mitochondrial epilepsy have been published. [ncbi.nlm.nih.gov]

  […] of the conditions and the reason for the encounter. progressive myoclonic epilepsy ( ICD-10-CM Diagnosis Code G40.3 Generalized idiopathic epilepsy and epileptic syndromes 2016 2017 2018 2019 Non-Billable/Non-Specific Code Code Also MERRF syndrome, if [icd10data.com]

• Vomiting

  […] abnormalities, a type of preexcitation syndrome known as Wolff-Parkinson-White syndrome, premature ventricular contractions, incomplete left bundle branch block and other, unrelated findings such as a short stature, lipomas, abdominal pain, recurrent vomiting [symptoma.com]

  […] prominent features: MELAS ( M itochondrial e ncephalomyopathy, L actic a cidosis, and S troke-like episodes) MERRF ( M yoclonic e pilepsy with R agged r ed f ibers) MELAS syndrome signs and symptoms: muscle weakness and pain recurrent headaches seizures vomiting [medschool.lsuhsc.edu]

  MELAS can lead to stroke-like episodes at a young age (usually before 40), seizures, dementia, headaches, vomiting, unsteadiness, and ill effects from exercise. [mitochondrialdiseases.org]

  Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) Onset: Childhood to early adulthood Symptoms: MELAS causes recurrent stroke-like episodes in the brain, migraine-type headaches, vomiting and seizures, and can lead to permanent [mda.org]

  The patient might have also had a gastrointestinal condition which could have been due to liver disease, as well as episodes of nausea or vomiting. [en.wikipedia.org]

• Nausea

  The patient might have also had a gastrointestinal condition which could have been due to liver disease, as well as episodes of nausea or vomiting. [en.wikipedia.org]

  […] headache/migraine, developmental delay, regression, dementia, tremo r, bradykinesia, retinopathy, optic atrophy, ophthalmoplegia Constitutional: exercise intolerance, growth failure, microcephaly, cachexia, lac tic acidosis, hyperalaninemia, SIDS GI: nausea [slideshare.net]

  She presented with a complex phenotype characterized by progressive cerebellar ataxia, frequent myoclonus seizures, recurrent stroke-like episodes, migraine-like headaches with nausea and vomiting, and elevated resting lactate blood level. [link.springer.com]

  […] psychiatrist, ophthalmologist There is no medication to slow the progression of the disease and treatments only target at controlling the symptoms Lactic acidosis is treated by sodium bicarbonate or sodium citrate Antiemetic drugs are used to treat nausea [lhsc.on.ca]

• Tachycardia

  Click Here to download this mito profile (PDF) Links: NINDS OMIM, X-linked: OMIM, Adult-onset: OMIM Symptoms: Hypermetabolism, with fever, heat intolerance, profuse perspiration, polyphagia, polydipsia, ragged-red fibers, and resting tachycardia. [umdf.org]

• Hearing Impairment

  Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. [ncbi.nlm.nih.gov]

  The disease also can cause hearing impairment and short stature. [mda.org]

  Hearing impairment is common in various phenotypes of the mitochondrial DNA A3243G mutation. Arch Neurol. 2001 Nov;58(11):1885-8. DiMauro S, Hirano M. MERRF. 2003 Jun 3 [updated 2015 Jan 29]. [ghr.nlm.nih.gov]

  Hearing impairment is common in various phenotypes of the mitochondrial DNA A3243G mutation. Arch Neurol. 2001; 58:1885–8. DOI: 10.1001/archneur.58.11.1885. PMID: 11708999. [ CrossRef ] [ Google Scholar ] 6. [e-sciencecentral.org]

• Night Blindness

  Symptoms LHON can result in complete blindness in one or both eyes, within about 6 months of initial symptoms. [lhsc.on.ca]

• Myopathy

  The human mitochondrial tRNA mutations are associated with a variety of diseases including mitochondrial myopathies. [en.wikipedia.org]

  Mitochondrial respiratory chain disorder Myoclonus epilepsy AND ragged red fibers Myoclonus epilepsy and ragged red fibers syndrome Myopathy, mitochondrial Neurogenic muscle weakness, ataxia and retinitis pigmentosa Pearson's syndrome R Kearns-Sayre [icd9data.com]

  Abstract A report is given of an association of dyssynergia cerebellaris myoclonica associated with Friedreich's ataxia and mitochondrial myopathy in 2 patients. [ncbi.nlm.nih.gov]

  Myopathy MTTL1 MM C3254G tRNA Leu (UUR) - + Rep ( 108 ) Mitochondrial Myopathy MTTL1 Myopathy A3280G tRNA Leu (UUR) - + Rep ( 68 ) Mitochondrial Myopathy MTTL1 Myopathy A3288G TRNA Leu(UUR) - + Rep ( 81 ) Mitochondrial Myopathy MTTI MM A4267G tRNA Ile [mitomap.org]

  Involuntary muscle twitches, generalized epilepsy, and cerebellar ataxia — these symptoms are typically indicative of a mitochondrial myopathy. [mitochondrialdiseasenews.com]

• Muscle Weakness

  Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. [ncbi.nlm.nih.gov]

  It also causes muscle weakness, with prominent effects on swallowing, speech and eye movements. [mda.org]

  […] pain recurrent headaches seizures vomiting abdominal pain hearing loss stroke-like episodes MERRF syndrome signs and symptoms: muscle twitches muscle weakness (abnormal muscle cells are ragged red figers) recurrent seizures uncoordinated movements hearing [medschool.lsuhsc.edu]

  Myoclonus is usually the first symptom followed by seizures, ataxia, muscle weakness and dementia. [rarediseases.org]

• Myoclonus

  […] fibers (disorder) Myoclonus epilepsy AND ragged red fibers (disorder) Myoclonus with epilepsy and with Ragged Red Fibers (MERRF syndrome) myoclonic epilepsy with ragged red fibers Fukuhara syndrome Myoclonus with epilepsy and with Ragged Red Fibers Myoclonic [wikidata.org]

  LEV may benefit myoclonus in PME of mitochondrial origin without altering mitochondrial function, and it could be considered the drug of first choice for the treatment of myoclonus in MERRF. [ncbi.nlm.nih.gov]

  The main trait of this disease is myoclonus, consisting of involuntary, brief, sudden spasms affecting extremities. [symptoma.com]

• Seizure

  The most frequent seizure type in MERRF is generalised myoclonic seizure but also focal myoclonic, focal atonic, generalised tonic-clonic, generalised atonic, generalised myoclonic-atonic, typical absences, or tonic-clonic seizures of unknown onset have [ncbi.nlm.nih.gov]

  The primary features displayed on a person with MERRF include myoclonus, seizures, cerebellar ataxia, myopathy, and ragged red fibers (RRF) on muscle biopsy, leading to the disease's name. [en.wikipedia.org]

  Individuals commonly experience myoclonic seizures, tonic-clonic seizures, and progressive neurological decline. Myoclonic seizures cause brief muscle twitching which often becomes more frequent over time. [disability-benefits-help.org]

  Ellie also suffers from seizures, muscle weakness and significant cognitive delays. [mitochondrialdiseases.org]

• Cerebellar Ataxia

  MERRF is characterized by myoclonic seizures (brief, sudden twitching muscle spasms), weakness (myopathy), cerebellar ataxia, progressive spasticity and dementia. [secure.ssa.gov]

  Diagnostic criteria for MERRF include typical manifestations of the disease: myoclonus, generalized epilepsy, cerebellar ataxia and ragged red fibers (RRF) on muscle biopsy. [scielo.br]

  The primary features displayed on a person with MERRF include myoclonus, seizures, cerebellar ataxia, myopathy, and ragged red fibers (RRF) on muscle biopsy, leading to the disease's name. [en.wikipedia.org]

  Abstract Myoclonic epilepsy and ragged-red fibers (MERRF) syndrome is a rare disorder characterized by myoclonus, muscle weakness, cerebellar ataxia, heart conduction block, and dementia. [ncbi.nlm.nih.gov]

  Patients usually present in late adolescence or early adulthood with 1-3 myoclonus epilepsy cerebellar ataxia intellectual disability vision and/or hearing loss cardiomyopathy with Wolff-Parkinson-White syndrome short stature The diagnosis of MERRF is [radiopaedia.org]

• Generalized Seizure

  Abstract Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a mitochondrial disorder characterized by myoclonus epilepsy, generalized seizures, ataxia and myopathy. [ncbi.nlm.nih.gov]

  At the age of 20 years, clear symptoms of MERRF syndrome developed, including myoclonic seizures, generalized tonic-clonic seizures, and paroxysmal hearing disturbance. [omim.org]

  Valproate is the first-line antiepileptic drug for generalized seizures and myoclonic epileptiform abnormalities 49. [doi.org]

• Limb Weakness

  Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) Onset: Usually before age 20 Symptoms: This disorder causes PEO, ptosis (droopy eyelids), limb weakness and gastrointestinal (digestive) problems, including chronic diarrhea and abdominal pain [mda.org]

  Exercise intolerance, limb weakness, hearing loss, and diabetes may also precede the occurrence of the stroke-like episodes. [umdf.org]

  Case report A 25-year-old male presented with paroxysmal left upper limb tics and weakness that had been ongoing for two years. [spandidos-publications.com]

  An individual with the MT-TF m.611G>A pathogenic variant had mild truncal and proximal limb weakness, cerebellar ataxia, bilateral Babinski sign, and frequent myoclonic jerks [ Mancuso et al 2004 ]. Table 2. [ncbi.nlm.nih.gov]

The diagnosis of MERRF is indicated by clinical examination and confirmed by molecular genetic testing and microscopic examination of the muscle biopsy specimen with modified Gomori trichrome or succinate dehydrogenase staining. This last method will show the presence of cytochrome c oxidase negative muscle fibers and ragged red fibers, while genetic tests will detect mitochondrial deoxyribonucleic acid mutations in white blood cells, urine, saliva, hair follicles, skin or muscle.

Blood workup reveals increased lactate and pyruvate concentrations in the blood and cerebrospinal fluid [10], which also has high protein concentration [11]. Creatine kinase levels may be slightly increased [12], but this is not a specific disease characteristic.

Brain imaging techniques like magnetic resonance imaging are able to diagnose stroke, brainstem atrophy [13], cerebellar atrophy [14] and basal ganglia calcification [15], while magnetic resonance spectroscopy detects brain lactate levels.

The electrocardiogram highlights rhythm and conduction abnormalities, if present. The electroencephalogram usually reveals generalized spike and wave discharges or focal epileptiform waves. The electromyogram and nerve conduction velocity may have either a myogenic or neurogenic aspect.

Genetic analysis may reveal MT-TL1, MT-TK, MT-TP, MT-TF or MT-TI mutations. Combined respiratory chain defects [16] and cytochrome c oxidase deficiency [17] have also been described.

• Epileptiform Activity

  The EEG of patients with MERRF usually exhibits variation in the degree of slowing of background activity and generalized epileptiform activity, which may worsen with intermittent photic stimulation 27, 33, 49, 50, 51. [doi.org]

  Generalized epileptiform discharges in 84.2% of patients, while focal discharges were present in ten patients. One of the patient had multifocal epileptiform activity. [bioline.org.br]

• Muscle Biopsy showing Ragged-Red Fibers

  Patients exhibit myoclonus epilepsy (involuntary muscle contractions) and show signs of ragged-red fibers in muscle biopsy. Less prevalent symptoms include deafness, exercise intolerance, dementia, and cardiomyopathies. [mitochondrialdiseasenews.com]

• Muscle Biopsy Abnormal

  Biopsy: Abnormal mitochondria from under the muscle tissue membrane appear as “ragged red fibres” under a microscope Chemical staining identifies diseased mitochondria, appearing as “ragged red fibres”. [lhsc.on.ca]

The treatment of progressive myoclonic epilepsy (PME) is largely empirical, even though valproic acid (VPA) is usually considered the drug of first choice. [ncbi.nlm.nih.gov]

Management and treatment As with other mitochondrial encephalomyopathies, there is no specific treatment for MERRF syndrome. [orpha.net]

There is very little success with these treatments as therapies in hopes of improving mitochondrial function. The treatment only alleviates symptoms, and these do not prevent the disease from progressing. [en.wikipedia.org]

Many genes are involved. [2] These include: MT-TK [3] MT-TL1 MT-TH [4] MT-TS1 [5] MT-TS2 MT-TF [6] Treatment Like many mitochondrial diseases, there is no cure for MERRF and treatment is primarily symptomatic. [ipfs.io]

Prognosis The prognosis for patients with MERRF syndrome is globally poor because of the progressive nature of the disease. [orpha.net]

Prognosis is generally quite poor. [lhsc.on.ca]

Prognosis The prognosis depends heavily on the underlying etiology and the epilepsy syndrome. Patients with a benign syndrome typically respond well to medication and may outgrow their epilepsy. [emedicine.medscape.com]

Genes involved include MT-TK, MT-TL1, MT-TH, MT-TS1, MT-TS2, and MT-TF. [1] Differentiating MERRF syndrome from Other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Diagnostic Criteria [wikidoc.org]

Prognosis - MERRF Syndrome Not supplied. Treatment - MERRF Syndrome The condition is caused by mutations - that can be detected with genetic testing in 90% of affected individuals - in the mitochondrial gene called MT-TK. [checkorphan.org]

Certain conditions have both an underlying etiology and multiple body system manifestations due to the underlying etiology. [icd10coded.com]

Etiology Seizures associated with early myoclonic encephalopathy can be due to a number of etiologies. [emedicine.medscape.com]

Etiology MERRF syndrome is caused by mutations in the mitochondrial DNA. Over 80% of individuals with MERRF syndrome carry the 8344A>G mutation in the lysine transfer RNA ( tRNA Lys ) gene ( MTTK ). [orpha.net]

Mitochondrial respiratory chain defects: underlying etiology in various epileptic conditions. Epilepsia. 2008 ;49: 685 – 690. Google Scholar | Crossref | Medline | ISI 19. Waldbaum, S, Patel, M. [doi.org]

Is the tRNA(Leu(UUR)) gene an etiologic hot spot? J Clin Invest. 1993 Dec;92(6):2906-15. Nakamura M, Nakano S, Goto Y, Ozawa M, Nagahama Y, Fukuyama H, Akiguchi I, Kaji R, Kimura J. [ghr.nlm.nih.gov]

The epidemiology of pathogenetic mitochondrial DNA mutations. Ann Neurol 2000 ; 48 : 188 –93. ↵ Darin N, Oldfors A, Moslemi A-R, et al. [jnnp.bmj.com]

Genes involved include MT-TK, MT-TL1, MT-TH, MT-TS1, MT-TS2, and MT-TF. [1] Differentiating MERRF syndrome from Other Diseases Epidemiology and Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Diagnostic Criteria [wikidoc.org]

Summary Epidemiology The prevalence in the general population of Europe has been estimated at 0.9 in 100 000, but the disease seems to be more common in the USA. [orpha.net]

Epidemiology The incidence of myoclonic epilepsy is approximately 1 case in 40,000 children. Typically, the onset of these disorders is during the first 3 years of life. [emedicine.medscape.com]

Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes: prevalence of the mutation in an adult population. [ncbi.nlm.nih.gov]

[…] following characteristics: progressive myoclonic epilepsy clumps of diseased mitochondria accumulate in the subsarcolemmal region of the muscle fiber and appear as "ragged-red fibers" when muscle is stained with modified Gomori trichrome stain short stature Pathophysiology [wikidoc.org]

This model is useful to clarify the pathophysiology and biomolecular mechanisms of MERRF syndrome. [nature.com]

Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological and biochemical characterization of a mitochondrial DNA disease. Cell. 1988 ;55: 601 – 610. Google Scholar | Crossref | Medline | ISI 13. [doi.org]

View Article : Google Scholar : PubMed/NCBI 5 De la Mata M, Garrido-Maraver J, Cotán D, et al: Recovery of MERRF fibroblasts and cybrids pathophysiology by coenzyme Q10. Neurotherapeutics. 9:446–463. 2012. [spandidos-publications.com]

Import of a tRNALys with a mutation in the anticodon preventing recognition of the lysine codons does not lead to any rescue, whereas downregulation of the transgenic tRNAs by small interfering RNA (siRNA) transiently abolishes the functional rescue, [ncbi.nlm.nih.gov]

Patients are usually prescribed therapeutic compounds to alleviate symptoms, but these do not prevent the disease from progressing. [mitochondrialdiseasenews.com]

Demographics Risk Factors Screening Natural History, Complications, and Prognosis Diagnosis Diagnostic Criteria History and Symptoms Physical Examination Laboratory Findings Imaging Findings Other Diagnostic Studies Treatment Medical Therapy Surgery Prevention [wikidoc.org]

Although higher proportions of the mutation in the blood of the mother result in a higher risk of having a child with severe phenotype, there are many examples of extreme segregation of the mutation from mother to child, which prevent efficient genetic [orpha.net]

Source: Genetics Home Reference, Wikipedia Prevention - MERRF Syndrome Not supplied. [checkorphan.org]

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