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Brain and Nerve = Shinkei Kenkyu No... Jan 2008MERRF is an acronym of myoclonus epilepsy associated with ragged-red fibers and was first reported as a new nosological entity belonging to mitochondrial... (Review)
Review
MERRF is an acronym of myoclonus epilepsy associated with ragged-red fibers and was first reported as a new nosological entity belonging to mitochondrial encephalomyopathies in San Remo symposium on "Mitochondrial Pathology" in 1982. MERRF was named Fukuhara disease by Rowland (1983). The first reported patient had been diagnosed as having Ramsay Hunt syndrome associated with Friedreich's ataxia. However, nowadays, the previously reported cases as having Ramsay Hunt syndrome associated with Friedreich's ataxia are regarded as having been suffered from MERRF. The history in establishing the nosological entity of MERRF was described. Patients with MERRF develop myoclonus, epileptic seizures, cerebellar ataxia, dementia, sensorineural hearing disturbance, optic atrophy, muscular wasting, and foot deformities at the advanced stage. Pathological findings show degeneration of the dentate nuclei, globus pallidus, and red nuclei, substantia nigra, inferior olivary nuclei, cerebellar cortex, and spinal cord. The posterior columns, the spinocerebellar tracts, and Clark's columns are degenerating in the spinal cord. The pyramidal tracts never show a severe degeneration as in Friedreich's ataxia. The skeletal muscles show mitochondrial abnormalities histologically and electron microscopically. Clinical features of MERRF are not necessarily uniform in the early stage and muscle biopsy findings are also very mild in some patients with MERRF, necessitating genetic analysis for diagnosis. Most of patients show a point mutation (A --> G) of nt 8344 in mitochondrial DNA.
Topics: Adult; Central Nervous System; DNA, Mitochondrial; Epilepsies, Myoclonic; Female; Humans; Japan; MERRF Syndrome; Male; Mitochondria, Muscle; Mitochondrial Encephalomyopathies; Point Mutation
PubMed: 18232333
DOI: No ID Found -
Journal of Neurology Mar 2003Mitochondrial cytopathies represent a heterogeneous group of multisystem disorders which preferentially affect the muscle and nervous systems. They are caused either by... (Review)
Review
Mitochondrial cytopathies represent a heterogeneous group of multisystem disorders which preferentially affect the muscle and nervous systems. They are caused either by mutations in the maternally inherited mitochondrial genome, or by nuclear DNA-mutations. Today, approximately 200 different disease causing mutations of mitochondrial DNA (mtDNA) are known, and due to the increased knowledge about nuclear genetics during the last few years, more and more nuclear mutations are being described. Owing to the non-uniform distribution of mitochondria in tissues and the co-existence of mutated and wildtype mtDNA (heteroplasmy) in these organelles, these disorders may present with a huge variety of symptoms, even if the same mutation is involved. Diagnostic investigations should include the measurement of serum and CSF lactate, neuroradiological tests and a muscle biopsy to show the characteristic ragged-red fibres and cytochrome c oxidase deficient cells and also to provide material for genetic analysis. To date, the treatment of these diseases remains supportive and should focus on typical complications such as cardiac dysrhythmia and endocrinopathy.
Topics: Animals; DNA, Mitochondrial; Humans; Kearns-Sayre Syndrome; Leigh Disease; MELAS Syndrome; MERRF Syndrome; Mitochondrial Myopathies; Ophthalmoplegia; Optic Atrophy, Hereditary, Leber
PubMed: 12638015
DOI: 10.1007/s00415-003-0978-3 -
BMJ Case Reports Mar 2021We present a rare case of myoclonic epilepsy with ragged red fibres with high level of heteroplasmy presenting with optic neuropathy and a rare phenotype of lipomatosis....
We present a rare case of myoclonic epilepsy with ragged red fibres with high level of heteroplasmy presenting with optic neuropathy and a rare phenotype of lipomatosis. Cutaneous lipomas are typically thought of as a benign/isolated entity and this case emphasises importance of considering mitochondrial disease in all patients with lipomatosis especially in the presence of other systemic abnormalities.
Topics: DNA, Mitochondrial; Humans; Lipomatosis; Lipomatosis, Multiple Symmetrical; MERRF Syndrome; Mutation; Optic Nerve Diseases
PubMed: 33766967
DOI: 10.1136/bcr-2020-240463 -
Archives of Neurology Nov 1993Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small... (Review)
Review
Mitochondrial diseases are uniquely interesting from a genetic point of view because mitochondria contain their own DNA (mtDNA) and are capable of synthesizing a small but vital set of proteins, all of which are components of respiratory chain complexes. Numerous mutations in mtDNA have been described in the past 5 years, and, it is, therefore, important for the clinician to keep in mind both some characteristic clinical presentations and, more importantly, some basic principles of "mitochondrial genetics," including heteroplasmy, the threshold effect, mitotic segregation, and maternal inheritance. The vast majority of mitochondrial proteins are encoded by nuclear DNA (nDNA) and have to be imported from the cytoplasm into mitochondria through a complex translocation machinery, which is also under the control of the nuclear genome. In addition, nDNA encodes several factors that control mtDNA replication, transcription, and translocation. Mitochondrial diseases due to mutations in nDNA are transmitted as mendelian traits and fall into three categories: (1) alterations of mitochondrial proteins; (2) alterations of mitochondrial protein importation; and (3) alterations of intergenomic communication. The first group of disorders can be further classified on the basis of the biochemical area affected, including defects of transport, defects of substrate utilization, defects of the Krebs cycle, defects of oxidation/phosphorylation coupling, and defects of the respiratory chain. The second group includes only few well-documented disorders but will certainly expand in the near future. The third group includes two conditions, an autosomal dominant form of progressive external ophthalmoplegia associated with multiple mtDNA deletions, and a quantitative defect of mtDNA (mtDNA depletion) causing severe infantile myopathy or hepatopathy.
Topics: Chromosome Deletion; Cytochrome-c Oxidase Deficiency; DNA; DNA Replication; DNA, Mitochondrial; Electron Transport Complex II; Electron Transport Complex IV; Humans; MELAS Syndrome; MERRF Syndrome; Mitochondrial Encephalomyopathies; Mitosis; Multienzyme Complexes; Mutation; NAD(P)H Dehydrogenase (Quinone); Optic Atrophies, Hereditary; Oxidoreductases; Point Mutation; Succinate Dehydrogenase
PubMed: 8215979
DOI: 10.1001/archneur.1993.00540110075008 -
Annals of Neurology Mar 2021
Topics: Aged; Ataxia; DNA, Mitochondrial; Genetic Testing; Humans; Lipomatosis; MERRF Syndrome; Magnetic Resonance Imaging; Male; Myoclonus; Neck
PubMed: 33341990
DOI: 10.1002/ana.25992 -
Acta Medica Portuguesa Jun 1994Mitochondrial Encephalomyopathies are primary disorders of energy metabolism recently described. They are the result of mitochondrial abnormalities with a wide spectrum... (Review)
Review
Mitochondrial Encephalomyopathies are primary disorders of energy metabolism recently described. They are the result of mitochondrial abnormalities with a wide spectrum of syndromes implying a multisystemic but predominantly muscular and cerebral involvement. Biochemical, histological, imagiologic and clinical features of the three well known mitochondrial syndromes (MERRF, MELAS and KSS) are described, as well as the mitochondrial genetics and maternal inheritance pattern.
Topics: Energy Metabolism; Humans; Mitochondria; Mitochondrial Encephalomyopathies; Syndrome
PubMed: 7942140
DOI: No ID Found -
Neurology May 2013Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial syndrome, mostly caused by the 8344A>G mitochondrial DNA mutation. Most of the previous studies...
OBJECTIVES
Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial syndrome, mostly caused by the 8344A>G mitochondrial DNA mutation. Most of the previous studies have been based on single case/family reports or series with few patients. The primary aim of this study was the characterization of a large cohort of patients with the 8344A>G mutation. The secondary aim was revision of the previously published data.
METHODS
Retrospective, database-based study (Nation-wide Italian Collaborative Network of Mitochondrial Diseases) and systematic revision.
RESULTS
Forty-two patients carrying the mutation were identified. The great majority did not have full-blown MERRF syndrome. Myoclonus was present in 1 of 5 patients, whereas myopathic signs and symptoms, generalized seizures, hearing loss, eyelid ptosis, and multiple lipomatosis represented the most common clinical features. Some asymptomatic mutation carriers have also been observed. Myoclonus was more strictly associated with ataxia than generalized seizures in adult 8344A>G subjects. Considering all of the 321 patients so far available, including our dataset and previously published cases, at the mean age of approximately 35 years, the clinical picture was characterized by the following signs/symptoms, in descending order: myoclonus, muscle weakness, ataxia (35%-45% of patients); generalized seizures, hearing loss (25%-34.9%); cognitive impairment, multiple lipomatosis, neuropathy, exercise intolerance (15%-24.9%); and increased creatine kinase levels, ptosis/ophthalmoparesis, optic atrophy, cardiomyopathy, muscle wasting, respiratory impairment, diabetes, muscle pain, tremor, migraine (5%-14.9%).
CONCLUSIONS
Our results showed higher clinical heterogeneity than commonly thought. Moreover, MERRF could be better defined as a myoclonic ataxia rather than a myoclonic epilepsy.
Topics: Adult; Age of Onset; DNA, Mitochondrial; Databases, Genetic; Disease Progression; Female; Humans; MERRF Syndrome; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Phenotype; Retrospective Studies
PubMed: 23635963
DOI: 10.1212/WNL.0b013e318294b44c -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023Patients with epilepsy who have also hearing loss represent a distinct group of patients, often with aggravated medical history, comorbidities and high potential for...
Patients with epilepsy who have also hearing loss represent a distinct group of patients, often with aggravated medical history, comorbidities and high potential for disability. The etiopathogenetic factors of epilepsy and hearing loss may be common to these conditions (neuroinfections, craniocerebral injuries, cerebral circulatory disorders, perinatal pathology, etc.). In addition, these two syndromes may occur as part of hereditary diseases, so their timely recognition and genetic diagnosis are important for determining further medical and genetic prognosis. This article provides an overview of orphan genetic diseases associated with epilepsy and hearing loss - MERRF syndrome, MELAS syndrome, EAST syndrome, Ayme-Grippsyndrome, epilepsy, hearing loss and mental retardation syndromes, associated with mutations in SPATA5 gene, DOOR syndrome, Gustavson syndrome.
Topics: Humans; Deafness; Epilepsy; Epileptic Syndromes; Hearing Loss; Hearing Loss, Sensorineural; Mutation
PubMed: 36719116
DOI: 10.17116/jnevro202312301128 -
Neurotherapeutics : the Journal of the... Apr 2012Mitochondrial DNA mutations are an important cause of human disease for which there is no effective treatment. Myoclonic epilepsy with ragged-red fibers (MERRF) is a...
Mitochondrial DNA mutations are an important cause of human disease for which there is no effective treatment. Myoclonic epilepsy with ragged-red fibers (MERRF) is a mitochondrial disease usually caused by point mutations in transfer RNA genes encoded by mitochondrial DNA. The most common mutation associated with MERRF syndrome, m.8344A > G in the gene MT-TK, which encodes transfer RNA(Lysine), affects the translation of all mitochondrial DNA encoded proteins. This impairs the assembly of the electron transport chain complexes leading to decreased mitochondrial respiratory function. Here we report on how this mutation affects mitochondrial function in primary fibroblast cultures established from patients harboring the A8344G mutation. Coenzyme Q10 levels, as well as mitochondrial respiratory chain activity, and mitochondrial protein expression levels were significantly decreased in MERRF fibroblasts. Mitotracker staining and imaging analysis of individual mitochondria indicated the presence of small, rounded, depolarized mitochondria in MERRF fibroblasts. Mitochondrial dysfunction was associated with increased oxidative stress and increased degradation of impaired mitochondria by mitophagy. Transmitochondrial cybrids harboring the A8344G mutation also showed CoQ10 deficiency, mitochondrial dysfunction, and increased mitophagy activity. All these abnormalities in patient-derived fibroblasts and cybrids were partially restored by CoQ10 supplementation, indicating that these cell culture models may be suitable for screening and validation of novel drug candidates for MERRF disease.
Topics: Cell Line; Cells, Cultured; Fibroblasts; Humans; MERRF Syndrome; Membrane Potential, Mitochondrial; Mutation; Ubiquinone
PubMed: 22354625
DOI: 10.1007/s13311-012-0103-3 -
European Heart Journal Oct 1996
Topics: Adolescent; Adult; Cardiomyopathy, Dilated; Female; Heart Failure; Heart Transplantation; Humans; MERRF Syndrome; Male; Mitochondria, Heart; Mitochondrial Myopathies
PubMed: 8909920
DOI: 10.1093/oxfordjournals.eurheartj.a014727