MERRF Syndrome
Lipomatosis, Multiple Symmetrical
MELAS Syndrome
RNA, Transfer, Lys
Epilepsies, Myoclonic
Mitochondrial Encephalomyopathies
RNA, Transfer, Leu
Kearns-Sayre Syndrome
A novel system for assigning the mode of inheritance in mitochondrial disorders using cybrids and rhodamine 6G. (1/51)
When normal human cultured skin fibroblasts were treated with the fluorescent dye rhodamine 6G (R6G), there was a drastic reduction in numbers of intact mitochondria and electron transport chain enzyme activities, despite the fact that mitochondrial DNA (mtDNA) was still present in treated cells. We used this observation to develop a novel system for generating cybrids. When cultured skin fibroblast cells from a patient with the mitochondrial encephalopathy and ragged-red fibers (MERRF) syndrome harboring the A8344G mtDNA mutation and which showed a severe reduction in cytochrome c oxidase activity were treated with R6G and fused to enucleated HeLaCOT cells, the resulting cybrid clones showed recovery of cytochrome c oxidase activity, and were shown to have mtDNA derived solely from the HeLaCOT cell line. R6G has significant advantages over ethidium bromide in removing the mitochondrial elements from cultured cells, and the results reported here demonstrate that this strategy can be used to determine the origin of the genetic defect in patients with electron transport chain abnormalities. (+info)Defective kinetics of cytochrome c oxidase and alteration of mitochondrial membrane potential in fibroblasts and cytoplasmic hybrid cells with the mutation for myoclonus epilepsy with ragged-red fibres ('MERRF') at position 8344 nt. (2/51)
We have investigated pathogenic effects of the tRNA(Lys) A8344G mutation associated with the syndrome myoclonus epilepsy with ragged-red fibres (MERRF) by using fibroblasts and fibroblast-derived cytoplasmic hybrid cells harbouring different percentages of mutated mitochondrial DNA (mtDNA). The activity of cytochrome c oxidase (COX) in patient fibroblasts with 89% mutated mtDNA was decreased to 20% of the control levels. COX exhibited altered kinetics, with a decreased V(max) for both the low-affinity and high-affinity phases; however, the K(m) values were not significantly changed. The substrate-dependent synthesis of ATP was decreased to 50% of the control. Analysis of the mitochondrial membrane potential, DeltaPsi, in digitonin-treated cells with tetramethylrhodamine methyl ester (TMRM) with the use of flow cytometry showed a 80% decrease in DeltaPsi at state 4 and an increased sensitivity of DeltaPsi to an uncoupler in fibroblasts from the patient. The investigation of transmitochondrial cytoplasmic hybrid clones derived from the patient's fibroblasts enabled us to characterize the relationship between heteroplasmy of the MERRF mutation, COX activity and DeltaPsi. Within the range of 87-73% mutated mtDNA, COX activity was decreased to 5-35% and DeltaPsi was decreased to 6-78%. These results demonstrate that the MERRF mutation affects COX activity and DeltaPsi in different proportions with regard to mutation heteroplasmy and indicate that the biochemical manifestation of the MERRF mutation exerts a very steep threshold of DeltaPsi inhibition. (+info)Apoptosis in mitochondrial encephalomyopathies with mitochondrial DNA mutations: a potential pathogenic mechanism. (3/51)
Mitochondrial encephalomyopathies caused by mitochondrial DNA (mtDNA) defects are a genetically and phenotypically heterogeneous group of disorders. The site, percentage and distribution of mutations do not explain the overall clinical heterogeneity that is found. Apoptosis (programmed cell death) is an evolutionarily conserved mechanism that is essential for tissue development and homeostasis. Dysregulation of apoptosis has been implicated in the pathogenesis of various human diseases, such as cancer and autoimmune and neurodegenerative disorders. Recent in vitro evidence has indicated the central role of mitochondria in the apoptotic process. We investigated the occurrence of apoptosis in muscle biopsies of 36 patients carrying different mtDNA mutations and four patients with inclusion body myositis and mitochondrial abnormalities. Apoptotic features, mainly localized in cytochrome c oxidase-negative fibres, were observed in muscle fibres of patients carrying a high percentage of single mtDNA deletions (>40%) and of tRNA point mutations (>70%). By contrast, no apoptotic changes were observed in inclusion body myositis and in patients carrying mutations of mtDNA structural genes. Our study suggests that apoptosis is not simply a means whereby cells with dysfunctional mitochondria are eliminated, but that it seems to play a role in the pathogenesis of mitochondrial disorders associated with mtDNA defects affecting mitochondrial protein synthesis. The imbalance and relative abundances of nuclear-encoded and mtDNA-encoded subunits may favour cytochrome c inactivation and release. Cytochrome c, together with respiratory chain dysfunction, could activate apoptotic pathways that, in turn, inhibit the rate of mitochondrial translation and the importation of nuclear-encoded mitochondrial protein precursors. This vicious circle may amplify the biochemical defects and tissue damage and contribute to the modulation of clinical features. (+info)Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNA(Lys) with the MERRF encephalomyopathy pathogenic mutation. (4/51)
A mitochondrial tRNA(Lys) gene mutation at nucleotide position 8344 is responsible for the myoclonus epilepsy associated with ragged-red fibers (MERRF) subgroup of mitochondrial encephalomyopathies. Here, we show that normally modified uridine at the anticodon wobble position remains unmodified in the purified mutant tRNA(Lys). We have reported a similar modification defect at the same position in two mutant mitochondrial tRNAs(Leu)(UUR) in another subgroup, mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), indicating this defect is common in the two kinds of tRNA molecules with the respective mutations of the two major mitochondrial encephalomyopathies. We therefore suggest the defect in the anticodon is responsible, through the translational process, for the pathogenesis of mitochondrial diseases. (+info)Cytochrome oxidase immunohistochemistry: clues for genetic mechanisms. (5/51)
Cytochrome c oxidase (COX) is encoded by three mitochondrial and nine nuclear genes. COX deficiency is genetically heterogeneous but current diagnostic methods cannot easily distinguish between mitochondrial and nuclear defects. We hypothesized that there may be differential expression of COX subunits depending on the underlying mutation. COX subunit expression was investigated in five patients with known mtDNA mutations. Severe and selective reduction of mtDNA-encoded COX subunits I and II was consistently observed in all these patients and was restricted to COX-deficient fibres. Immunostaining of nuclear-encoded subunits COX IV and Va was normal, whilst subunit VIc, also nuclear-encoded, was decreased. Twelve of 36 additional patients with histochemically defined COX deficiency also had this pattern of staining, suggesting that they had mtDNA defects. Clinical features in this group were heterogeneous, including infantile encephalopathy, multisystem disease, cardiomyopathy and childhood-onset isolated myopathy. The remaining patients did not have the same pattern of immunostaining. Fourteen had reduced staining of all subunits, whilst 10 had normal staining of all subunits despite reduced enzyme activity. Patients with COX deficiency secondary to mtDNA mutations have a specific pattern of subunit loss, but the majority of children with COX deficiency do not have this pattern of subunit loss and are likely to have nuclear gene defects. (+info)Simultaneous A8344G heteroplasmy and mitochondrial DNA copy number quantification in myoclonus epilepsy and ragged-red fibers (MERRF) syndrome by a multiplex molecular beacon based real-time fluorescence PCR. (6/51)
The association of a particular mitochondrial DNA (mtDNA) mutation with different clinical phenotypes is a well-known feature of mitochondrial diseases. A simple genotype-phenotype correlation has not been found between mutation load and disease expression. Tissue and intercellular mosaicism as well as mtDNA copy number are thought to be responsible for the different clinical phenotypes. As disease expression of mitochondrial tRNA mutations is mostly in postmitotic tissues, studies to elucidate disease mechanisms need to be performed on patient material. Heteroplasmy quantitation and copy number estimation using small patient biopsy samples has not been reported before, mainly due to technical restrictions. In order to resolve this problem, we have developed a robust assay that utilizes Molecular Beacons to accurately quantify heteroplasmy levels and determine mtDNA copy number in small samples carrying the A8344G tRNA(Lys) mutation. It provides the methodological basis to investigate the role of heteroplasmy and mtDNA copy number in determining the clinical phenotypes. (+info)Wobble modification defect in tRNA disturbs codon-anticodon interaction in a mitochondrial disease. (7/51)
We previously showed that in mitochondrial tRNA(Lys) with an A8344G mutation responsible for myoclonus epilepsy associated with ragged-red fibers (MERRF), a subgroup of mitochondrial encephalomyopathic diseases, the normally modified wobble base (a 2-thiouridine derivative) remains unmodified. Since wobble base modifications are essential for translational efficiency and accuracy, we used mitochondrial components to estimate the translational activity in vitro of purified tRNA(Lys) carrying the mutation and found no mistranslation of non-cognate codons by the mutant tRNA, but almost complete loss of translational activity for cognate codons. This defective translation was not explained by a decline in aminoacylation or lowered affinity toward elongation factor Tu. However, when direct interaction of the codon with the mutant tRNA(Lys) defective anticodon was examined by ribosomal binding analysis, the wild-type but not the mutant tRNA(Lys) bound to an mRNA- ribosome complex. We therefore concluded that the anticodon base modification defect, which is forced by the pathogenic point mutation, disturbs codon- anticodon pairing in the mutant tRNA(Lys), leading to a severe reduction in mitochondrial translation that eventually could result in the onset of MERRF. (+info)Histochemical and molecular genetic study of MELAS and MERRF in Korean patients. (8/51)
Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode (MELAS) and myoclonic epilepsy and ragged-red fibers (MERRF) are rare disorders caused by point mutation of the tRNA gene of the mitochondrial genome. To understand the pathogenetic mechanism of MELAS and MERRF, we studied four patients. Serially sectioned frozen muscle specimens with a battery of histochemical stains were reviewed under light microscope and ultrastructural changes were observed under electron microscope. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed and the tRNA genes were sequenced to confirm mutations. In two patients with MELAS, strongly succinyl dehydrogenase positive blood vessels (SSVs) and many cytochrome oxidase (COX) positive ragged-red fibers (RRFs) were observed, and A3243G mutations were found from the muscle samples. In two patients with MERRF, neither SSV nor COX positive RRFs were seen and A8344G mutations were found from both muscle and blood samples. In the two MERRF families, the identical mutation was observed among family members. The failure to detect the mutation in blood samples of the MELAS suggests a low mutant load in blood cells. The histochemical methods including COX stain are useful for the confirmation and differentiation of mitochondrial diseases. Also, molecular biological study using muscle sample seems essential for the confirmation of the mtDNA mutation. (+info)Myoclonic Epilepsy with Ragged Red Fibers (MERRF) is a rare mitochondrial disorder, which is a group of genetic disorders that affect the energy production within cells. It is characterized by multiple symptoms including myoclonus (jerky, involuntary muscle spasms), epilepsy (recurrent seizures), ataxia (lack of coordination and balance), dementia, and weakness. The name "MERRF" comes from the characteristic finding of "ragged red fibers" in muscle biopsies when viewed under a microscope using special stains. These fibers are abnormal muscle cells containing clusters of abnormal mitochondria. MERRF is caused by mutations in the mitochondrial DNA, most commonly the A8344G point mutation in the MT-TK gene. It is typically inherited from the mother and can affect multiple organs throughout the body.
Multiple Symmetrical Lipomatosis is a rare condition characterized by the growth of multiple, symmetrical fatty tumors (lipomas) beneath the skin. These lipomas are typically slow-growing and benign, but their large number and symmetric distribution can lead to significant cosmetic concerns and, in some cases, functional impairment.
The tumors usually develop on the neck, shoulders, back, and abdomen, and they may also occur on the arms and legs. While the exact cause of Multiple Symmetrical Lipomatosis is not known, it has been associated with alcohol abuse and metabolic disorders. Treatment typically involves surgical removal of the lipomas, although this can be challenging due to their number and location. Recurrence of the tumors is also common.
A syndrome, in medical terms, is a set of symptoms that collectively indicate or characterize a disease, disorder, or underlying pathological process. It's essentially a collection of signs and/or symptoms that frequently occur together and can suggest a particular cause or condition, even though the exact physiological mechanisms might not be fully understood.
For example, Down syndrome is characterized by specific physical features, cognitive delays, and other developmental issues resulting from an extra copy of chromosome 21. Similarly, metabolic syndromes like diabetes mellitus type 2 involve a group of risk factors such as obesity, high blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels that collectively increase the risk of heart disease, stroke, and diabetes.
It's important to note that a syndrome is not a specific diagnosis; rather, it's a pattern of symptoms that can help guide further diagnostic evaluation and management.
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome is a rare inherited mitochondrial disorder that affects the body's energy production mechanisms. It is characterized by a combination of symptoms including recurrent headaches, vomiting, seizures, vision loss, hearing impairment, muscle weakness, and stroke-like episodes affecting primarily young adults.
The condition is caused by mutations in the mitochondrial DNA (mtDNA), most commonly the A3243G point mutation in the MT-TL1 gene. The symptoms of MELAS syndrome can vary widely among affected individuals, even within the same family, due to the complex inheritance pattern of mtDNA.
MELAS syndrome is typically diagnosed based on a combination of clinical features, laboratory tests, and genetic testing. Treatment is supportive and aimed at managing individual symptoms as they arise.
I'm happy to help! Here are the definitions for each of those terms:
1. RNA (Ribonucleic Acid): RNA is a nucleic acid that plays a crucial role in the process of gene expression. It carries genetic information from DNA to the ribosomes, where proteins are synthesized. RNA is made up of a long chain of nucleotides, just like DNA, but with some key differences in its structure and composition.
2. Transfer: In the context of biochemistry, "transfer" refers to the movement or transport of molecules from one location to another within a cell or between cells. This process is often facilitated by specific proteins or other molecular carriers.
3. Lys (Lysine): Lysine is an essential amino acid that cannot be synthesized by the human body and must be obtained through diet. It plays important roles in various biological processes, including protein synthesis, enzyme function, hormone production, and energy metabolism. In molecular biology, lysine is often used as a marker for certain types of modifications to proteins or nucleic acids.
Therefore, "RNA, Transfer, Lys" could refer to the transfer RNA (tRNA) molecule that carries a specific amino acid, such as lysine, to the ribosome during protein synthesis. The tRNA molecule recognizes a specific codon on the messenger RNA (mRNA) and brings the corresponding amino acid to the growing polypeptide chain, allowing for the translation of genetic information into a functional protein.
Myoclonic epilepsies are a group of epilepsy syndromes characterized by the presence of myoclonic seizures. A myoclonic seizure is a type of seizure that involves quick, involuntary muscle jerks or twitches. These seizures can affect one part of the body or multiple parts simultaneously and may vary in frequency and severity.
Myoclonic epilepsies can occur at any age but are more common in infancy, childhood, or adolescence. Some myoclonic epilepsy syndromes have a genetic basis, while others may be associated with brain injury, infection, or other medical conditions.
Some examples of myoclonic epilepsy syndromes include:
1. Juvenile Myoclonic Epilepsy (JME): This is the most common type of myoclonic epilepsy and typically begins in adolescence. It is characterized by myoclonic jerks, often occurring upon awakening or after a period of relaxation, as well as generalized tonic-clonic seizures.
2. Progressive Myoclonic Epilepsies (PME): These are rare inherited disorders that typically begin in childhood or adolescence and involve both myoclonic seizures and other types of seizures. PMEs often progress to include cognitive decline, movement disorders, and other neurological symptoms.
3. Lennox-Gastaut Syndrome (LGS): This is a severe form of epilepsy that typically begins in early childhood and involves multiple types of seizures, including myoclonic seizures. LGS can be difficult to treat and often results in cognitive impairment and developmental delays.
4. Myoclonic Astatic Epilepsy (MAE): Also known as Doose syndrome, MAE is a childhood epilepsy syndrome characterized by myoclonic seizures, atonic seizures (brief periods of muscle weakness or loss of tone), and other types of seizures. It often responds well to treatment with antiepileptic drugs.
The management of myoclonic epilepsies typically involves a combination of medication, lifestyle changes, and, in some cases, dietary modifications. The specific treatment plan will depend on the type of myoclonic epilepsy and its underlying cause.
Mitochondrial Encephalomyopathies are a group of genetic disorders that primarily affect the mitochondria, which are the energy-producing structures in cells. "Encephalo" refers to the brain, while "myopathy" refers to muscle disease. Therefore, Mitochondrial Encephalomyopathies are conditions that cause both neurological and muscular symptoms due to impaired mitochondrial function.
These disorders can affect any organ in the body, but they primarily impact the brain, nerves, and muscles. Symptoms may include muscle weakness, seizures, developmental delays, hearing loss, vision loss, heart problems, and lactic acidosis (a buildup of lactic acid in the blood).
Mitochondrial Encephalomyopathies can be caused by mutations in either the mitochondrial DNA or nuclear DNA. They are often inherited from the mother, as mitochondria are passed down through the maternal line. However, some cases can also result from new mutations that occur spontaneously.
Due to the complex nature of these disorders and their varying symptoms, diagnosis and treatment can be challenging. Treatment typically focuses on managing specific symptoms and may include medications, dietary changes, and physical therapy.
A transfer RNA (tRNA) molecule that carries the amino acid leucine is referred to as "tRNA-Leu." This specific tRNA molecule recognizes and binds to a codon (a sequence of three nucleotides in mRNA) during protein synthesis or translation. In this case, tRNA-Leu can recognize and pair with any of the following codons: UUA, UUG, CUU, CUC, CUA, and CUG. Once bound to the mRNA at the ribosome, leucine is added to the growing polypeptide chain through the action of aminoacyl-tRNA synthetase enzymes that catalyze the attachment of specific amino acids to their corresponding tRNAs. This ensures the accurate and efficient production of proteins based on genetic information encoded in mRNA.
Kearns-Sayre Syndrome (KSS) is a rare, progressive genetic disorder that affects the function of the mitochondria, which are the energy-producing structures in cells. It is classified as a type of mitochondrial myopathy and is typically associated with symptoms that appear before the age of 20.
The medical definition of Kearns-Sayre Syndrome includes the following criteria:
1. Onset before 20 years of age
2. Progressive external ophthalmoplegia (PEO), which is characterized by weakness and paralysis of the eye muscles, leading to drooping eyelids (ptosis) and limited eye movement
3. Retinitis pigmentosa, a degenerative condition affecting the retina that can lead to vision loss
4. A cardiac conduction defect, such as heart block
5. Ragged red fibers on muscle biopsy
6. At least one major criteria or two minor criteria must be present:
* Major criteria include cerebellar ataxia (lack of coordination), deafness, or increased protein in the cerebrospinal fluid
* Minor criteria include pigmentary retinopathy, heart block, or a high level of creatine kinase in the blood.
Kearns-Sayre Syndrome is caused by a single large-scale deletion of genes in the mitochondrial DNA and is usually sporadic, meaning it occurs randomly and is not inherited from parents. The condition can be diagnosed through genetic testing, muscle biopsy, or other clinical tests. Treatment is focused on managing symptoms and may include physical therapy, surgery for ptosis, hearing aids, and pacemakers for heart block.
MERRF syndrome
MT-TF
Mitochondrial encephalomyopathy
MT-TK
Heteroplasmy
Myoclonic epilepsy
Mitochondrial DNA
MT-TL1
MT-TH
Non-coding RNA
Unverricht-Lundborg disease
Epilepsy syndromes
Mitochondrial optic neuropathies
Mitochondrial disease
List of MeSH codes (C10)
MELAS syndrome
Glutamate receptor
Progressive myoclonus epilepsy
List of MeSH codes (C18)
Mitochondrion
List of syndromes
MT-ND5
List of MeSH codes (C05)
List of neuromuscular disorders
Mitochondrial myopathy
Myoclonus
List of diseases (M)
List of MeSH codes (C16)
List of ICD-9 codes 240-279: endocrine, nutritional and metabolic diseases, and immunity disorders
MERRF syndrome - Wikipedia
Myoclonic epilepsy with ragged-red fibers: MedlinePlus Genetics
Myoclonus epilepsy with ragged-red fibers: a clinical and electrophysiologic follow-up study on two sibling cases
MELAS Syndrome: Background, Pathophysiology, Epidemiology
Mitochondrial disorders testing - Oxford University Hospitals
John Libbey Eurotext - Epileptic Disorders - Selective deep brain stimulation in the substantia nigra reduces myoclonus in...
JCI Insight - Heteroplasmic and homoplasmic m.616T|C in mitochondria tRNAPhe promote isolated chronic kidney disease and...
Rareshare
Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial...
WebMD Epilepsy Guide - Better Information for Better Health
Bio2Vec
Mitochondrial DNA Abnormalities - Special Subjects - MSD Manual Professional Edition
MERRF: Myoclonus Epilepsy Ragged-red Fibers | North American Mitochondrial Disease Consortium
Myoclonus in mitochondrial disorders<...
MT-TH Gene | Encyclopedia MDPI
International Classification of Diseases - Endocrine, Nutritional and Metabolic Diseases, and Immunity Disorders
Severity of Diabetes in MELAS and MERRF May Rather Reflect Genotype and Comorbidities than Histology of Islet Cells| Himalayan...
Strokes in mitochondrial diseases | Pizova | Neurology, Neuropsychiatry, Psychosomatics
MELAS Syndrome Medication: Vitamins and dietary supplements
Symptomatic Generalized Epilepsy Clinical Presentation: History, Physical Examination, Causes
What Post-Pandemic Looks Like for Us as the Family of a Child With a Rare Disease
ClinVar for MedGen (Select 44095) - ClinVar - NCBI
The long road to diagnosis - News - The Lily Foundation for research into Mitochondrial Disease and other metabolic disorders
Mitochondrial disorders | MedLink Neurology
Coenzyme Q10 / Ubiquinol / Ubiquinone - a comprehensive guide to therapeutic use
Pesquisa | Biblioteca Virtual em Saúde - BRASIL
Biopolymers and Cell
Maureen Newman, Author at Mitochondrial Disease News - Page 2 of 2
Myoclonic10
- MERRF syndrome (or myoclonic epilepsy with ragged red fibers) is a mitochondrial disease. (wikipedia.org)
- Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. (medlineplus.gov)
- abstract = "Myoclonus is a possible manifestation of mitochondrial disorders, and its presence is considered, in association with epilepsy and the ragged red fibers, pivotal for the syndromic diagnosis of MERRF (myoclonic epilepsy with ragged red fibers). (unicatt.it)
- Finally, this study reinforces the notion that myoclonus is not inextricably linked to epilepsy in MERRF patients, and therefore the term {"}myoclonic epilepsy{"} seems inadequate and potentially misleading. (unicatt.it)
- As mentioned above, a few individuals with a mutation in the MT-TH gene have features of both myoclonic epilepsy with ragged-red fibers (MERRF) and MELAS. (encyclopedia.pub)
- myoclonic epilepsy and ragged-red fibers (MERRF) syndrome, and Kearns-Sayre syndrome (sporadic multisystem mitochondrial pathology). (ima-press.net)
- In Ohtahara syndrome, tonic spasms are the dominant seizure type, with little to no myoclonic seizures. (medscape.com)
- Specific syndromes of progressive myoclonic epilepsy with key clinical features include Unverricht-Lundborg disease (Baltic myoclonus), myoclonus epilepsy with ragged red fibers (MERRF), neuronal ceroid lipofuscinoses (Batten disease), and sialidoses (cherry-red spot myoclonus syndrome). (medscape.com)
- If myoclonic epilepsy with ragged red fibers (MERRF) syndrome is caused by at least one of four point mutations in mitochondrial DNA, then curing the disease should be as easy as giving new mitochondria to patients. (mitochondrialdiseasenews.com)
- optic neuropathy) and MERRF (myoclonic epilepsy with ragged red fibers) are what kind of genetic disorder? (brainscape.com)
MELAS and MERRF3
- MT-TH gene mutations that cause MELAS and MERRF/MELAS overlap syndrome change single DNA building blocks (nucleotides) in the gene. (encyclopedia.pub)
- First, MELAS and MERRF are completely different disorders, why simply the genotype can explain the difference between the two patients. (himjournals.com)
- Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF. (ima-press.net)
Myopathy5
- 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. (wikipedia.org)
- MERRF is characterized by muscle twitches (myoclonus), weakness (myopathy), and progressive stiffness (spasticity). (medlineplus.gov)
- Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome is a multisystem and progressive neurodegenerative disorder. (medscape.com)
- Strokelike episodes and mitochondrial myopathy characterize MELAS syndrome. (medscape.com)
- For individuals with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome and for those with other oxidative phosphorylation (OXPHOS) disorders, metabolic therapies are administered to increase the production of adenosine triphosphate (ATP) and to slow or arrest the deterioration of this condition and other mitochondrial encephalomyopathies. (medscape.com)
Mutations12
- The cause of MERRF disorder is due to mutations in the mitochondrial genome. (wikipedia.org)
- Four point mutations in the genome can be identified that are associated with MERRF: m.A8344G, m.T8356C, m.G8361A, and m.G8363A. (wikipedia.org)
- The remaining mutations only account for 10% of cases, and the remaining 10% of the patients with MERRF did not have an identifiable mutation in the mitochondrial DNA. (wikipedia.org)
- Mutations in the MT-TK gene are the most common cause of MERRF, occurring in more than 80 percent of all cases. (medlineplus.gov)
- Less frequently, mutations in the MT-TL1 , MT-TH , and MT-TS1 genes have been reported to cause the signs and symptoms of MERRF. (medlineplus.gov)
- People with mutations in the MT-TL1 , MT-TH , or MT-TS1 gene typically have signs and symptoms of other mitochondrial disorders as well as those of MERRF. (medlineplus.gov)
- Mutations that cause MERRF impair the ability of mitochondria to make proteins, use oxygen, and produce energy. (medlineplus.gov)
- A small percentage of MERRF cases are caused by mutations in other mitochondrial genes, and in some cases the cause of the condition is unknown. (medlineplus.gov)
- Most cases of MERRF are maternally inherited due to mtDNA mutations. (rarediseasesnetwork.org)
- Four other mitochondrial DNA mutations have been reported to cause MERRF. (rarediseasesnetwork.org)
- MERRF syndrome is caused by mutations in mitochondrial DNA, which in sperm cells is typically lost during fertilisation, so all mtDNA comes from the mother. (thelilyfoundation.org.uk)
- For example, Leigh syndrome is associated with over 30 gene mutations, making it difficult to use single-gene identification as a cost-effective means of pinpointing Leigh syndrome. (mitochondrialdiseasenews.com)
Mutation10
- The causes of MERRF syndrome are difficult to determine, but because it is a mitochondrial disorder, it can be caused by the mutation of nuclear DNA or mitochondrial DNA. (wikipedia.org)
- The point mutation m.A8344G is most commonly associated with MERRF, in a study published by Paul Jose Lorenzoni from the Department of neurology at University of Panama stated that 80% of the patients with MERRF disease exhibited this point mutation. (wikipedia.org)
- Less commonly, the disorder results from a new mutation in a mitochondrial gene and occurs in people with no family history of MERRF. (medlineplus.gov)
- Approximately 80% of patients with the clinical characteristics of MELAS syndrome have a heteroplasmic A-to-G point mutation in the dihydrouridine loop of the transfer RNA (tRNA) Leu (UUR) gene at base pair (bp) 3243 (ie, 3243 A → G mutation). (medscape.com)
- This mutation is commonly associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS). (nih.gov)
- No diabetic subject was shown to have the mtDNA mutation at position 8344 (tRNA(lys)) which has previously been described in the syndrome of mitochondrial encephalomyopathy and red-ragged fibres (MERRF). (nih.gov)
- The most common MERRF mutation is A8344G, which accounted for over 80% of the cases (GeneReview article). (rarediseasesnetwork.org)
- The mutation involved in this overlap syndrome replaces the nucleotide guanine with the nucleotide adenine at gene position 12147 (written as G12147A). (encyclopedia.pub)
- It remains unknown why this mutation causes the overlapping features of MERRF and MELAS. (encyclopedia.pub)
- Guillian-Barre syndrome has an extra AT in TATA box, which reduces the expression by 80%, because of this type of mutation? (brainscape.com)
Seizures2
- Other features of MERRF include recurrent seizures (epilepsy), difficulty coordinating movements (ataxia), a loss of sensation in the extremities (peripheral neuropathy), and slow deterioration of intellectual function (dementia). (medlineplus.gov)
- The absence seizures involved in this syndrome are often prolonged, with bilateral limb myoclonus, differentiating it from idiopathic childhood absence seizures, for which seizure duration involves seconds and can be accompanied with only mild jerks of eyes, eyelids, or eyebrows. (medscape.com)
Lactic acidosis1
- The typical presentation of patients with MELAS syndrome includes features that comprise the name of the disorder, such as mitochondrial encephalomyopathy, lactic acidosis , and strokelike episodes. (medscape.com)
MtDNA1
- Researchers have not determined how changes in mtDNA lead to the specific signs and symptoms of MERRF. (medlineplus.gov)
Epilepsy3
- Finally, myoclonus is not inextricably linked to epilepsy in MERRF patients, but more to cerebellar ataxia. (unicatt.it)
- Epilepsy syndromes that are included in the category of SGE are discussed below. (medscape.com)
- Finsterer J. Photosensitive Epilepsy and Polycystic Ovary Syndrome as Manifestations of MERRF. (clinicalcases.eu)
Kearns-Sayre Sy2
- If patients with Kearns-Sayre syndrome commonly are deficient in folate, logic would presume folinic acid therapy may benefit their symptoms. (mitochondrialdiseasenews.com)
- Chronic progressive external ophthalmoplegia (CPEO) is the most common characteristic of Kearns-Sayre syndrome, which is one member of the family of mitochondrial myopathies. (mitochondrialdiseasenews.com)
Multisystem1
- The multisystem dysfunction in patients with MELAS syndrome may be due to both parenchymal and vascular OXPHOS defects. (medscape.com)
Symptoms8
- Most patients will not exhibit all of these symptoms, but more than one of these symptoms will be present in a patient who has been diagnosed with MERRF disease. (wikipedia.org)
- Due to the multiple symptoms presented by the individual, the severity of the syndrome is very difficult to evaluate. (wikipedia.org)
- In most cases, people with MERRF inherit an altered mitochondrial gene from their mother, who may or may not show symptoms of the disorder. (medlineplus.gov)
- The prognosis for MERRF varies widely depending on age of onset, type and severity of symptoms, organs involved, and other factors. (rarediseasesnetwork.org)
- This combination of signs and symptoms is called MERRF/MELAS overlap syndrome. (encyclopedia.pub)
- Researchers have not determined how these genetic changes alter energy production in mitochondria or cause the varied signs and symptoms of MELAS or MERRF/MELAS overlap syndrome. (encyclopedia.pub)
- In addition, L-arginine may modulate excitation by neurotransmitters at nerve endings and such effects might contribute to alleviation of strokelike symptoms in MELAS syndrome. (medscape.com)
- Even if two individuals are affected by the same disease, such as Leigh syndrome, they may not have identical symptoms or causes of disease. (mitochondrialdiseasenews.com)
Dementia3
- Ragged-red fibers (a characteristic microscopic abnormality observed in muscle biopsy of patients with MERRF and other mitochondrial disorders) Additional manifestations may include: hearing loss, short stature, exercise intolerance, dementia, multiple lipomas (fat tumors under the skin), cardiac defects, eye abnormalities, and speech impairment. (rarediseasesnetwork.org)
- Approximately 55 percent were felt to have a single progressive neurodegenerative etiology, predominantly Alzheimer disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), dementia related to Parkinson disease (PD), and corticobasal degeneration (including corticobasal syndrome and many other phenotypes) [ 2 ]. (medilib.ir)
- The remaining 45 percent of patients had the following etiologies: vascular-related cognitive change, alcohol-related cognitive change, Huntington disease (HD), cognitive impairment resulting from multiple sclerosis (MS), prion diseases, dementia related to Down syndrome (predominantly AD), and unknown/unclassified. (medilib.ir)
Disorder that affects1
- Estrella Salazar is a 17-year-old science genius from Nezahualcoyotl, Mexico whose 25-year-old sister, Perla, was born with MERRF syndrome, a rare disorder that affects the nervous system and can cause issues with hearing and mobility. (hiplatina.com)
Phenotypes1
- The regional brain metabolic abnormalities in patients with these syndromes showed different features consistent with the distinct phenotypes. (neurology.org)
Characterize1
- Malformation syndromes characterize various major and minor physical abnormalities with distinctive type of facial features. (epainassist.com)
Affects2
- MERRF syndrome affects different parts of the body, particularly the muscles and nervous system. (wikipedia.org)
- For Harry's mother Mandy Norris, finding out that her son had MERRF syndrome, a mitochondrial disease that affects the muscles and nervous system, came with the added blow of learning that he had inherited the causal gene from her. (thelilyfoundation.org.uk)
Ataxia1
- Diagnosis and Management of Opsoclonus-Myoclonus-Ataxia Syndrome in Children: An International Perspective. (nih.gov)
Cardiomyopathy1
- Noonan syndrome is a common type of malformation syndrome case takes place with pediatric type of cardiomyopathy. (epainassist.com)
Disorders5
- Mitochondrial disorders, including MERRF, may present at any age. (wikipedia.org)
- MERRF is part of a group of conditions known as mitochondrial disorders, which affect an estimated 1 in 5,000 people worldwide. (medlineplus.gov)
- As with all mitochondrial disorders, there is no cure for MERRF. (rarediseasesnetwork.org)
- Capsule?CAPD: Continuous ambulatory peritoneal dialysis?Caps: Capsules?CAPS: Cryopyrin-Associated Periodic Syndromes disorders?CAPTIA Syph G: ?CAPTIA Syph M: ?CAST: Cardiac arrhythmia suppression trials?CAT: Computerized axial tomography?Cataplasm. (kuwaitpharmacy.com)
- Mitochondrial DNA Depletion Syndrome (MDDS) is a group of autosomal recessive disorders that can lead to a significant reduction in the amount of mitochondrial DNA in affected tissues (e.g. muscle, liver, brain). (mitochondrialdisease.nhs.uk)
Strokelike episodes5
- The pathogenesis of the strokelike episodes in MELAS syndrome has not been completely elucidated. (medscape.com)
- The unusual strokelike episodes and higher morbidity observed in MELAS syndrome may be secondary to alterations in nitric oxide homeostasis that cause microvascular damage. (medscape.com)
- Arginine administration during the acute and interictal periods of the strokelike episodes of the MELAS syndrome may represent a potential new therapy to reduce brain damage due to mitochondrial dysfunction, and is one of the most promising therapies to date. (medscape.com)
- Based on the hypothesis that the strokelike episodes in MELAS syndrome are triggered by impaired vasodilation in the intracerebral arteries due to decreased levels of circulating NO, elevation of arginine and NO levels may ameliorate this effect. (medscape.com)
- May be beneficial for treatment/prevention of strokelike episodes in MELAS syndrome. (medscape.com)
Mitochondrial myopathies1
- The category even includes mitochondrial abnormalities, like MERRF, MELAS, diseases in respiratory system or chain, defects in fatty acid oxidation, mitochondrial myopathies and Barth or Pompe syndromes. (epainassist.com)
Manifestations1
- The clinical manifestations of PCOS can be exacerbated by post-COVID syndrome. (clinicalcases.eu)
Patients6
- An individual displaying MERRFs syndrome will manifest not only a single symptom, but patients regularly display more than one affected body part at a time. (wikipedia.org)
- It has been observed that patients with MERRF syndrome will primarily display myoclonus as a first symptom. (wikipedia.org)
- Measurements of respiratory enzyme activities in intact mitochondria have revealed that more than one half of the patients with MELAS syndrome may have complex I or complex I + IV deficiency. (medscape.com)
- In MERRF, only one of four patients showed an increase in the lactate/creatine resonance intensity ratio (an index of impairment of oxidative metabolism) in spectra from central (supraventricular) or occipital brain volumes, and this was small. (neurology.org)
- Treatment with CoQ10 has been helpful in some patients with MELAS syndrome. (medscape.com)
- Patients with traumatic brain injury, Down syndrome, and certain types of vascular disease are major patient groups that may or may not be included in these studies. (medilib.ir)
Diagnosis3
- Lumpers" include virtually any type of SGE, whereas "splitters" require slow spike-wave complexes to make a diagnosis of Lennox-Gastaut syndrome. (medscape.com)
- Challenges in diagnosis and understanding of natural history of polycystic ovary syndrome. (clinicalcases.eu)
- Congenital central hypoventilation syndrome: diagnosis and management. (nih.gov)
Features3
- The features of MERRF vary widely among affected individuals, even among members of the same family. (medlineplus.gov)
- Study of this patient and his siblings showed a distinct form of late-onset diabetes associated with nerve deafness but no clinical features of the MELAS syndrome. (nih.gov)
- X;Y translocation in a girl with short stature and some features of Turner's syndrome: cytogenetic and molecular studies. (clinicalcases.eu)
Genetic4
- Harry had his genetic blood test there in August 2016, and in November we got confirmation that yes, it was MERRF. (thelilyfoundation.org.uk)
- The etiology of polycystic ovary syndrome (PCOS) is not exactly known, but there are indications that genetic factors, exposure to androgen in early childhood, and obesity lead to a disruption of the hypothalamic-pituitary-ovarian axis and dysregulation of microRNAs. (clinicalcases.eu)
- Trisomy 21 (down syndrome) is an example of what kind of genetic disorder? (brainscape.com)
- Turner syndrome (45X) is what kind of genetic disorder? (brainscape.com)
Fatty1
- Less commonly, people with MERRF develop fatty tumors, called lipomas, just under the surface of the skin. (medlineplus.gov)
Childhood1
- MERRF is a progressive multi-system syndrome presenting in childhood or in adulthood. (rarediseasesnetwork.org)
Dysfunction1
- Finsterer J. Mitochondrial Dysfunction in Polycystic Ovary Syndrome. (clinicalcases.eu)
Abnormality1
- Yet another pattern of regional metabolic abnormality was present in the MELAS syndrome, where proton spectroscopic imaging demonstrated focal localization of abnormally increased lactate/creatine and decreased N -acetylaspartate/creatine to the regions of the stroke-like lesions on conventional MR images. (neurology.org)
Depletion1
- In secondary carnitine deficiency associated with MELAS syndrome, carnitine may restore generation of free CoA and avoid carnitine depletion. (medscape.com)
Genes1
- Ear drops?AutoPap: Computer-assisted cytology interpretation system?AV: Aortic valve?AV: Atrioventricular?A-V: Arteriovenous?AVERT: Atorvastatin Versus Revascularization treatment?AVID: ?AVM: Arteriovenous Malformation?AVNRT: AV nodal reentry tachycardia?AVP: Arginine vasopressin?AVR: Aortic valve replacement?AVR: Augmented V lead, right arm (ECG)?AVRT: ?AVS: Arteriovenous shunt?AWS: Alcohol withdrawal syndrome?AXR: Abdominal X ray?AZF: Azoospermia factor genes?AZT: Azidothymidine (zidovudine)?B & O: Belladonna and opium?B Bx. (kuwaitpharmacy.com)