There are several specific considerations regarding anesthesia in patients with mitochondrial disease. Fukuhara had already proposed the name merrf for a syndrome comprising myoclonic epilepsy and ragged red fibers on muscle biopsy. Anesthetic considerations in patients presenting with. A 29yearold female with progressive myoclonus and cognitive. It is an xlinked trait characterized by epilepsy and the overproduction of the lactase enzyme. The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes melas syndrome represents one of the most frequent mitochondrial disorders. The mutation involved in this overlap syndrome replaces the nucleotide guanine with the nucleotide adenine at. Four died during the acute episodes, and the survivors never had a recurrence.
The feasibility of delivering mitochondria using the cellpenetrating peptide pep1 for the treatment of merrf myoclonic epilepsy with ragged red fibers syndrome, which is caused by point mutations in the transfer rna genes of mitochondrial dna, is examined further using cellular models derived from patients with merrf syndrome. Detects four mtdna point mutations linked to merrf syndrome typical presentation. Regionalized pathology correlates with augmentation of mtdna copy numbers in a patient with myoclonic epilepsy with raggedred fibers merrf syndrome 20 october 2010 plos one, vol. 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 is a maternally inherited disease that is characterized by myoclonic epilepsy, cerebellar ataxia and progressive muscular weakness. 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 syndrome affects different parts of the body, particularly the muscles and nervous system. Regionalized pathology correlates with augmentation of mtdna copy numbers in a patient with myoclonic epilepsy with raggedred fibers merrfsyndrome 20 october 2010 plos one, vol. Which of the following statements is true regarding merrf syndrome. 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. Myoclonus epilepsy associated with raggedred fibers. 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.
Myoclonic epilepsy with raggedred fibers without increased. Myoclonic epilepsy with ragged red fibers genetic and. Melas syndrome and merrf syndrome school of medicine. Melas and merrf syndromes are two disorders caused by mitochondrial mutations. As with other mitochondrial disorders, treatment is supportive. This multisystem disorder is characterized clinically by strokelike episodes. Merrf syndrome definition of merrf syndrome by the free. Upregulation of matrix metalloproteinase 1 and disruption. The ph gradients are not shown for the mutant cells energised. Pdf myoclonic epilepsy with raggedred fibers merrf clinical. The distinguishing feature in merrf is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. Features may include myoclonus, ataxia, weakness, seizures, hearing loss and ragged red fibers.
May 04, 2015 after the first patients were diagnosed with merrf in 1973, researchers have been working to understand the pathology and cause of the disease. Decreased atp synthesis is phenotypically expressed during. Over the years, the few point mutations in mtdna that have been found in patients with merrf have usually. 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. Mitochondria are the main producers of atp needed for normal electrical activities of neurons and synaptic transmission. Pathogenic mutations in the mitochondrial trna lys may cause the merrf syndrome. Acute infantile liver failure due to mutations in the trmu gene. Merrf syndrome is a mitochondrial disease this video contains general medical information if in doubt, always seek professional medical advice.
A group of symptoms that collectively indicate or characterize a disease, disorder, or other condition considered abnormal. Merrf syndrome definition of merrf syndrome by medical. Anesthetic management of a patient with merrf syndrome. You can view this document in free acrobat reader, navigate through the page or. Merrf syndrome synonyms, merrf syndrome pronunciation, merrf syndrome translation, english dictionary definition of merrf syndrome. When should merrf myoclonus epilepsy associated with.
Here we describe an individual with characteristic features of merrf along with symmetric thalamic lesions, which are uncommon in. Wellcome trust centre for mitochondrial research newcastle uk. The progressive myoclonic epilepsies pmes are a group of symptomatic generalised epilepsies caused by rare disorders, most of which have a genetic component, a debilitating course, and a poor outcome. The myoclonic epilepsy and raggedred fiber mutation. However, this is a theoretical treatment easier said then done because delivering mitochondria to deficient cells within the human body is a difficult task. Myoclonus epilepsy associated with raggedred fibers merrf. Accurate detection and quantitation of heteroplasmic. The cellular machinery for energy metabolism comprises the krebs cycle, fatty acid oxidation and oxidative phosphorylation all of which are found within the mitochondria.
Pathogenic mitochondrial dna mutations have been identified in the mitochondrial transfer rna trnalys at positions 8344 and 8356. 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. Melas syndrome patients with melas syndrome usually appear healthy at birth with normal early development, then exhibit delayed growth, episodic vomiting, seizures, and recurrent cerebral injuries resembling stroke. 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.
Treatment for patients with the 8344ag merrf mutation really involves trying to make sure that we minimise the impact of the disease on peoples lives. This was a challenging case, with a broad differential diagnosis that included a madelung disease, also known as benign symmetric lipomatosis, multiple symmetric lipomatosis, and launoisbensaude syndrome. Merrf syndrome is a rare disorder that affects males and females in equal numbers. Pdf file format, developed by adobe systems, represents in electronic mode all the elements of a printed document such as text, photos, links, scales, graphs and interactive elements. Merrf syndrome nord national organization for rare. 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 red ragged fibres merrf is a rare mitochondrial disorder presenting with progressive myoclonus, epilepsy, and cognitive decline. Challenges with pme arise from difficulty with diagnosis, especially in the early stages of the illness, and further problems of management and drug treatment.
Of these, perhaps the beststudied is the ag transition at position 8344 in the trnalys gene, the mutation that causes myoclonic epilepsy and raggedred fiber syndrome merrf. May 01, 2015 merrf syndrome is a mitochondrial disease this video contains general medical information if in doubt, always seek professional medical advice. Here, the authors present a case of a 29yearold lady presenting with myoclonus and describe the subsequent investigations that led to a diagnosis of merrf. After the first patients were diagnosed with merrf in 1973, researchers have been working to understand the pathology and cause of the disease. Myoclonic epilepsy with ragged red fibers merrf has mitochondrial or maternal inheritance. Juichih chang, lead author of the article treatment of human cells derived from merrf syndrome by. 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.
Enable javascript to view the expandcollapse boxes. In addition, we examine her cognitive decline over a 9year period, demonstrating a. Myoclonic epilepsy associated with raggedred fibers is one of the mitochondrial encephalomyopathies. The g8363a point mutation appears to be related to the presence of cardiomyopathy and deafness in patients with merrf, and, in some cases, it overlap with leigh syndrome15,18,19,20.
The winnower myoclonic epilepsy with raggedred fibers merrf. Merrf is a progressive mitochondrial disorder associated with prominent. Symmetric thalamic lesions in a patient with a myoclonic. Her son, who also carried the mutation, had merrf syndrome. Polymerase chain reaction pcr, restriction fragment length polymorphism rflp reference range. By screening for the genes with altered levels of expression, we first discovered that matrix metalloproteinase 1 mmp1. Common findings are hearing loss, short stature, optic atrophy, and cardiomyopathy with wolffparkinsonwhite wpw syndrome. 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. Human mitochondrial deoxyribonucleic acid dna is a doublestranded circular molecule that encodes 37 gene products proteins, 2 ribonucleic acids and 22 transfer ribonucleic acids over 16 569 base pairs. A detailed description of the individual disorders that compose these groups, such as kearnssayre syndrome, merrf syndrome myoclonus epilepsy with ragged red fibers, and melas syndrome mitochondrial encephalopathy, myopathy, lactic acidosis, and strokelike episodes, is beyond the scope of this chapter. The melas syndrome was first described by pavlakis et al. Jan 11, 2005 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.
Histochemical and molecular genetic study of melas and merrf. The medical information is not advice and should not. Myoclonic epilepsy with raggedred fibers merrf syndrome is a rare syndromic. The features of merrf vary widely among affected individuals, even among members of the same family. Myoclonic epilepsy and ragged red fibers merrf syndrome.
It is a mitochondrial disease that only appears in females, given that mitochondria are transmitted through the cytoplasm of female gametes. Introduction human mitochondrial dna mtdna is a doublestranded, 16. Anesthetic management of a patient with merrf syndrome article in pediatric anesthesia 151. The features of merrf vary widely among affected individuals, even among members of the same family merrf is characterized by muscle twitches myoclonus.
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. Management of epilepsy in merrf syndrome seizure european. Apr 06, 2015 the present study further illustrates the feasibility of mitochondrial intervention therapy using the novel approach of peptidemediated mitochondrial delivery and the benefit resulting from mitochondriaorganelle manipulation, wrote dr. Common findings are hearing loss, short stature, optic atrophy, and cardiomyopathy with wolffparkinsonwhite wpw. Patients with merrf can additionally exhibit recurrent seizures, difficulty coordinating movements, peripheral neuropathy and the slow deterioration.
Autosomal dominant, autosomal recessive, and xlinked inheritance could be excluded. Melas syndrome and kidney disease without fanconi syndrome. Onset is usually in childhood, occurring after normal early development. Additionally, they have a central role in neurotransmitter synthesis, calcium homoeostasis. Kidney involvement usually manifests as fanconi syndrome or focal segmental. Treatment of human cells derived from merrf syndrome by. By screening for the genes with altered levels of expression, we first discovered that matrix metalloproteinase 1 mmp1 was highly induced in the primary culture of skin. Symptoms usually first appear in childhood or adolescence after normal early development. One affected individual with merrfmelas overlap syndrome had two pathogenic. Merrf is characterized by myoclonic seizures brief, sudden twitching muscle spasms, weakness myopathy, cerebellar ataxia, progressive spasticity and dementia. Myoclonic epilepsy with ragged red fibers merrf syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers in skeletal muscle.
Pdf myoclonic epilepsy with raggedred fibers merr f is an ultrarare mitochondrial disease, typically associated with a point mutation of. Acute liver failure in infancy accompanied by lactic acidemia was previously shown to result from mtdna depletion. Merrf syndrome nord national organization for rare disorders. Merrf myoclonic epilepsy with ragged red fibers syndrome is a. Some reasonably welldefined disorders include melas syndrome, kearnsayre syndrome, leigh disease, and merrf syndrome, table 1. When should merrf myoclonus epilepsy associated with ragged. The myoclonic epilepsy and raggedred fiber mutation provides. 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. Variability of expression and variable characteristics of the inheritance were consistent with mutation in mitochondrial dna. Danielle mercer 1, fern tsien 2, and barbara gordonwendt 1. It is called maternal inheritance because mitochondrial dna are inherited from maternally inherited egg cells, but not from paternally inherited sperm cells. Certainly it is important to make sure that people have adequate treatment for their seizures, both the myoclonic jerks and the tonic clonic seizures. The present study reports the case of a 25yearold male who presented with paroxysmal left upper limb tics and weakness for two years.
This disorder is an encephalomyopathy characterized by myoclonic. Patients exhibit myoclonus epilepsy involuntary muscle contractions and show signs of raggedred fibers in muscle biopsy. The fraction of mutant mtdna in the woman varied between 62% and 80% in cultured skin fibroblasts, lymphocytes, normal adipose tissue, and muscle, whereas the fraction of mutant mtdna in the lipomas ranged from 90 to 94%. Myoclonic epilepsy with raggedred fibers merrf is a neurological disorder that is characterized by muscle twitches, weakness and progressive stiffness that affects numerous muscles of the body. We report on unrelated infants who presented with acute liver failure and lactic acidemia with normal mtdna content. Acute infantile liver failure due to mutations in the trmu. 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. The merrf syndrome is most commonly the result of a single base pair substitution at. As mentioned above, a few individuals with a mutation in the mtth gene have features of both myoclonic epilepsy with raggedred fibers merrf and melas.
The features of merrf vary widely from individual to individual, even within families. The methods employed in making the correct diagnosis, the preoperative patient assessment and correction of metabolic dysfunctions and anaesthetic techniques used, are highlighted. Upregulation of matrix metalloproteinase 1 and disruption of. Myoclonic epilepsy with ragged red fibers genetic and rare. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. 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. Merrf myoclonic epilepsy with ragged red fibers is a multisystem disorder. Characteristics of myoclonic epilepsy associated with raggedred fibers include myoclonic epilepsy, generalized epilepsy, hearing loss, exercise intolerance. Seizures are often the key manifestation of neurological diseases caused by pathogenic mutations in 169 of the genes that have so far been identified to affect mitochondrial function. Histochemical and molecular genetic study of melas and.
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