Myoclonic epilepsy with ragged red fibers merrf is a rare inherited neurometabolic disorder that affects the central nervous system, skeletal muscles, and other body systems. Merrf syndrome is a rare disorder that affects males and females in equal numbers. Anesthetic management of a patient with merrf syndrome. Jun 03, 2003 merrf myoclonic epilepsy with ragged red fibers is a multisystem disorder characterized by myoclonus often the first symptom followed by generalized epilepsy, ataxia, weakness, and dementia. Myoclonic epilepsy with raggedred fibers merrf genedx. Merrf myoclonic epilepsy with ragged red fibers is an inherited. Ideal sources for wikipedia s health content are defined in the guideline wikipedia. Merrf syndrome, also known as myoclonus epilepsy with raggedred fibers is a very rare multisystem disorder, part of the mitochondrial encephalomyopathies cluster, due to mitochondrial abnormalities mutations in mitochondrial deoxyribonucleic acid that mainly affects the muscular and nervous systems and becomes symptomatic during childhood or adolescence, affecting patients in an unequal. Merrf is a rare panethnic mitochondrial disease which is caused by mutations in the mtdna it mainly affects the muscle tissue and the nervous system onset can range from childhood to adulthood, but typically symptoms show after a normal early development as one ages, symptoms start progressing. You obtain a detailed family history from this patient and produce pedigree you realize affected mother to. Nuclear dnaencoded trnas targeted into mitochondria can. Clinical and brain mr imaging features focusing on the.
She also showed mental deterioration, muscle atrophy weakness, and truncal ataxia. Recovery of merrf fibroblasts and cybrids pathophysiology. Over 80% of individuals with merrf syndrome carry the 8344ag mutation in the. It is important that healthcare providers monitor individuals with melas syndrome on a regular basis for disease progression. Merrf typically begins in childhood, but adultonset has been reported hirano 2008. Diagnostic criteria for merrf include typical manifestations of the disease. Apr 06, 2015 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. Myoclonus epilepsy usually manifesting earlierthan in our patient, sensorineural hearing loss,premature graying, and rrf on muscle biopsy arefeatures of the merrf syndrome. Weve been blessed to see michael lead a normal life, earning his boy scout eagle award and being inducted into the national honor society. Merrf syndrome definition of merrf syndrome by medical. The features of merrf vary widely among affected individuals, even among members of the same family. Pathogenic mutations in the mitochondrial trna lys may cause the merrf syndrome.
Mar 16, 2016 myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes melas onset. Merrf myoclonus epilepsy with raggedred 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. Myoclonic epilepsy with raggedred fibers merrf is a disorder that affects many parts of the body, particularly the muscles and nervous system. Myoclonic epilepsy with raggedred fibers merrf is a rare mitochondrial syndrome, mostly caused by the 8344ag mitochondrial dna mutation. We describe the successful administration of a combined general and epidural anesthesia with sevoflurane maintenance in a patient with myoclonic epilepsy with ragged red fibers merrf syndrome scheduled for surgical treatment of bilateral clubfoot. Frontiers overlapping leigh syndromemyoclonic epilepsy. Pathology of skeletal muscle fibers and small blood vessels.
There are several specific considerations regarding anesthesia in patients with mitochondrial disease. Myoclonic epilepsy with ragged red fibers genetic and rare. Here are links to possibly useful sources of information about merrf syndrome. A, ct scan with contrast shows gyriform enhancement pattern to right parietal lobe with central hypodensity. Variability of expression and variable characteristics of the inheritance were consistent with mutation in mitochondrial dna.
The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. Myoclonus epilepsy associated with raggedred fibers merrf. However, a few cases of melas or merrf syndromeassociated with the clinical presentationofkss. Files are available under licenses specified on their description page. Before the wide availability of genetic testing the common merrf mutations were. Pdf merrf syndrome presenting with multiple symmetric. Merrf is characterized by myoclonic seizures brief, sudden twitching muscle spasms, weakness myopathy, cerebellar ataxia, progressive spasticity and dementia. The merrf diagnostic criteria described in 1980 by fukuhara et al included as typical manifestations of the dis. Over 80% of individuals with merrf syndrome carry the 8344ag mutation in the lysine transfer rna trna lys gene mttk.
The full text of this article is available in pdf format. Merrf syndrome should be diagnosed by correlation of its heterogeneous clinical and genetic features, in order to improve the quality of life of these patients. The hallmarks of melas are encephalomyopathy with seizures andor dementia, lactic acidosis a buildup of lactic acid in the body, and. If a mother has a mutation in her mitochondrial dna, all of her children will inherit the mutation and may or may not have symptoms. Merrf syndrome myoclonic epilepsy with ragged red fibres. Myoclonic epilepsy with ragged red fibers merrf has mitochondrial or maternal inheritance. Merrf is one of the most common mitochondrial encephalomyopathies. Weve discovered that no one can predict exactly how michaels or jennifers cases will progress. To our knowledge, this is the first reported case of overlapping leigh syndromemerrf in an adolescent patient. Molecular genetic analysis of mitochondrial dna revealed the adenine to guanine transition at position 8344 in the trna gene for lysine that has been associated with the myoclonic epilepsy and ragged red fiber merrf syndrome. When should merrf myoclonus epilepsy associated with ragged. They may be associated with merrf melas overlap syndrome, in which affected individuals also suffer from strokelike episodes. Importantly, the amount of coq, an essential electron. Since the mitochondria affect so many things in the cell, mitochondrial diseases manifest in many different ways, and as such, mitochondrial disease life expectancy is hard to predict as a general term.
Merrf syndrome, commonly associated with an origination in childhood is described as a multisystem disease that is characterized by spontaneous muscle contractions, generalized epilepsy, loss of control regarding bodily movements, dementia and weakness. Her son, who also carried the mutation, had merrf syndrome. Myoclonic epilepsy with raggedred fibers merrf syndrome is a rare syndromic. Melas syndrome one of the family of mitochondrial cytopathies, which also include merrf, and lebers hereditary optic neuropathy. May 04, 2015 a group from universidade federal do parana in brazil asked the question, when should merrf myoclonus epilepsy associated with raggedred fibers be the diagnosis, and identified some of the clinical and laboratory manifestations associated with merrf.
The merrf fibroblasts showed reduced expression and activity of the mitochondrial respiratory chain complexes, as has been previously reported. These main characteristic features provide a goodclue in differ entiating these syndromes. He specializes in the evaluation, diagnosis and treatment of developmental delay, neurodegeneration and metabolic disease. Myoclonus epilepsy with raggedred fibers springerlink. In 80% of cases, merrf is caused by a single base pair mutation a changes to g in mitochondrial dna mtdna, at location 8344. Pdf treatment of human cells derived from merrf syndrome. Merrf syndrome synonyms, merrf syndrome pronunciation, merrf syndrome translation, english dictionary definition of merrf syndrome. Conventional brain mr imaging showed atrophy of the superior cerebellar peduncles and the cerebellum in all patients and brain stem atrophy in 2 patients. We report 3 patients with myoclonic epilepsy with raggedred fibers merrf diagnosed by mitochondrial a8344g mutation.
Having an illness that affect the mitochondrial does not mean that the child should have autism or. Impaired ros scavenging system in human induced pluripotent stem cells generated from patients with merrf syndrome skip to main content thank you for visiting. Specically, the patient appeared to have an overlap syndrome with features of both merrf and kss. Management of epilepsy in merrf syndrome seizure european. Autosomal dominant, autosomal recessive, and xlinked inheritance could be excluded.
In this work, we studied the pathophysiology of the m. Onset is usually in childhood, occurring after normal early development. Jun 16, 2015 since the mitochondria affect so many things in the cell, mitochondrial diseases manifest in many different ways, and as such, mitochondrial disease life expectancy is hard to predict as a general term. Danielle mercer 1, fern tsien 2, and barbara gordonwendt 1.
Merrf syndrome nord national organization for rare disorders. 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. Understanding mitochondrial disorders cleveland clinic. Patient 1 afflicted with the leigh syndrome had experienced neurological deterioration and psychomotor regression since 14 years of age. Acronym for myoclonus epilepsy with raggedred fibers. Frontiers molecular diagnosis of myoclonus epilepsy. Mar 01, 2000 using an assay that combines trna oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wildtype trnas in tissue samples from patients with melas syndrome mito.
All structured data from the file and property namespaces is available under the. The merrf syndromeis characterized bymyoclonicep ilepsy with cerebellar ataxia, and melas by strokelike episodes with headache, nausea, and vomiting. Cerebellar ataxia was the first symptom in all patients. Myoclonic epilepsy with ragged red fibers merrf is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. Pdf myoclonic epilepsy with ragged red fibers merrf, also called fukuharas disease, is sometimes accompanied by the rare symptom of multiple. Which of the following statements is true regarding merrf syndrome. Our aim was to determine whether the a8344g mitochondrial trna lys mutation, which can cause the merrf myoclonic epilepsy with raggedred fibers syndrome, could be complemented by targeting trnas into mitochondria from the cytosol. Myoclonus epilepsy associated with raggedred fibers. In these circumstances, merrf can only be diagnosed using genetic analyses. Symptoms usually first appear in childhood or adolescence after normal early development. Myoclonic epilepsy with ragged red fibers genetic and.
Peptidemediated mitochondrial delivery for merrf treatment. Impaired ros scavenging system in human induced pluripotent stem cells generated from patients with merrf syndrome. Lactate levels in both blood and cerebrospinal fluid were elevated. May 01, 2015 symptoms, risk factors and treatments of merrf syndrome medical condition merrf syndrome is a mitochondrial disease this video contains general medical information if in doubt, always seek. It is a mitochondrial disease that only appears in females, given that mitochondria are transmitted through the cytoplasm of female gametes. Merrf is a progressive mitochondrial disorder associated with prominent myoclonus. Having an illness that affect the mitochondrial does not mean that the child should have autism or brain diseases. A read is counted each time someone views a publication summary such as the title, abstract, and list of authors, clicks on a figure, or views or downloads the fulltext. The distinguishing feature in merrf is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. We hypothesise that the course of the phenotype of this family begins with merrf and is followed by melas.
Many individuals with merrf take a vitamin compound with coenzyme q10 and other vitamins that may increase the mitochondrias ability to produce energy. Jan 14, 2010 sumit parikh, md, is a neurometabolic and neurogenetics staff clinician at cleveland clinic. Treatment of human cells derived from merrf syndrome by peptidemediated mitochondrial delivery. Myoclonic epilepsy with ragged red fibers merrf free download as powerpoint presentation. As described, merrf melas overlap syndrome may also caused by a double pathogenic mutation in mitochondrial trna genes m. Merrf syndrome wikipedia a rare mitochondrial disease characterized by progressive myoclonic epilepsy and clumps of diseased mitochondria that accumulate in the subsarcolemmal region of the muscle fiber and appear as ragged red fibers when stained.
However, this is a theoretical treatment easier said then done because. Merrf syndrome european journal of paediatric neurology. Mitochondrial disease life expectancy and expectations. A diagnosis of merrf syndrome can guide appropriate genetic counselling. The relationship between mutation load and clinical phenotypes. The trip database provides clinical publications about evidence. Melas syndrome and merrf syndrome school of medicine. Sep, 2018 in three of these four cases, merrf developed prior to the age of 7, with leigh syndrome occurring 511 years later. The winnower myoclonic epilepsy with raggedred fibers merrf. Mitochondrial dna g8363a mutation in the trnalys gene. It was also the first disorder that linked an epilepsy syndrome to a molecular defect. Mitochondrial transfer from whartons jelly mesenchymal. The features of merrf vary widely from individual to individual, even within families. Myoclonus was present in 1 of 5 patients, whereas myopathic signs and symptoms.
Myoclonic epilepsy with raggedred fibers myoclonic epilepsy with raggedred fibers merrf is a multisystem disorder in which the cardinal symptoms of pme are associated with typical myopathy with raggedred fibers seen on muscle biopsy, indicating dysfunction of the mitochondrial respiratory chain. Results phenotypes of the four patients were merrf, merrf melas overlap syndrome and asymptomatic carrier. Yes are approved or conditionally approved by new york state and do not require an nys npl exemption. Sep 29, 2017 myoclonus epilepsy with raggedred fibers merrfs, an inherited mitochondrial disorder, has characteristic morphological changes of raggedred fibers rrfs in muscle biopsy, in the absence of which mitochondrial etiology is usually not considered in patients with phenotypes suggestive of merrf. The g8363a is a very rare mtdna trna lys gene mutation that has been associated to merrf like syndrome, cardiomyopathy or leigh syndrome. Myoclonus epilepsy with raggedred fibers merrf is a multisytemic mitochondrial syndrome fukuhara 1991. Myoclonus is one of the typical features of merrf syndrome, defined as myoclonic epilepsy with ragged red fibers, or maybe more.
Smaller areas of focal atrophy are noted in right anterior frontal, left frontal, and left parietal lobes. Merrf syndrome nord national organization for rare. Other mutations have been found in other transfer rna genes or in the mtnd5 gene. Merrf and kearnssayre overlap syndrome due to the mtdna m. In the examined case of merrf syndrome, skeletal muscle pathology was compared with the pathology of small blood vessels, capillaries, and arterioles, at the ultrastructural level. However, our patient developed leigh syndrome and merrf almost simultaneously as an adolescent. Parkinmediated mitophagy and autophagy flux disruption in. Myoclonus epilepsy usually manifesting earlier than in our patient, sensorineural hearing loss, premature graying and raggedred fibers on muscle biopsy are features of the merrf syndrome.
Merrf syndrome is a rare, maternally inherited, multisystemic mitochondrial disease, which is caused in about 80% of cases by the m. The most characteristic symptom is myoclonic seizures that are usually sudden, brief, jerking spasms that can affect the limbs or the entire body. Jun 15, 2016 cases of the month merrf and kearnssayre overlap syndrome due to the mitochondrial dna m. Belongs to a group of rare muscular disorders called mitochondrial encephalomyopathies. Mitochondrial dna mtdna mutations are an important cause of human disease for which there is no efficient treatment. Merrf syndrome or myoclonic epilepsy with ragged red fibers is a mitochondrial disease.
It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. Merrf syndrome definition of merrf syndrome by the free. Melas and merrf syndromes are two disorders caused by mitochondrial mutations. Parikh is the codirector of the cleveland clinic mitochondrial clinic and the cyclic vomiting syndrome clinic. Phenotypic heterogeneity of the 8344ag mtdna merrf. It is extremely rare, with an estimated prevalence of 1400,000 in europe, and has varying degrees of expressivity owing to heteroplasmy. Decreased aminoacylation of mutant trnas in melas but not in. At the age of 20 years, clear symptoms of merrf syndrome developed, including myoclonic seizures, generalized tonicclonic seizures, and paroxysmal hearing disturbance. These disorders are passed on from the mother, and cannot be inherited by. Specifically, the patient appeared to have an overlap syndrome with features of both merrf and kss. This double mutation was heteroplasmic in blood of all four patients but with different rates in each patient, while m. It is called maternal inheritance because mitochondrial dna are inherited from maternally inherited egg cells, but not from paternally inherited sperm cells. Abstract myoclonic epilepsy associated with ragged red fibers merrf is a rare mitochondrial disorder. Like most of mitochondrial diseases, there is no specific cure for merrf syndrome and the treatments are principally symptomatic.
A 23yearold female presents with progressive bilateral loss of central vision. Myoclonic epilepsy with raggedred fibers merrf new york clients tests displaying the status new york approved. The disease was so named because the patients all had myoclonus epilepsy and mitochondrialdysfunction wasfound uponmuscle biopsy2. Myoclonus and epilepsy, most often medically intractable epilepsy, are hallmarks of the illness. When should merrf myoclonus epilepsy associated with. Merrf syndrome affects different parts of the body, particularly the muscles and nervous system. Merrf syndrome is one of the mitochondrial encephalomyopathies and the clinical phenotypes and mechanism of pathogenesis of this disease has been studied for more than three decades. The acronym, merrf, or myoclonus epilepsy and ragged red fiber disease, represents one of the early mitochondrial syndromes, whose molecular genetic basis was first established in 1990 by shoffner and coworkers.
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