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Gayathri N, Deepha S, Sharma S. Diagnosis of primary mitochondrial disorders -Emphasis on myopathological aspects. Mitochondrion 2021; 61:69-84. [PMID: 34592422 DOI: 10.1016/j.mito.2021.09.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 09/03/2021] [Accepted: 09/22/2021] [Indexed: 12/29/2022]
Abstract
Mitochondrial disorders are one of the most common neurometabolic disorders affecting all age groups. The phenotype-genotype heterogeneity in these disorders can be attributed to the dual genetic control on mitochondrial functions, posing a challenge for diagnosis. Though the advancement in the high-throughput sequencing and other omics platforms resulted in a "genetics-first" approach, the muscle biopsy remains the benchmark in most of the mitochondrial disorders. This review focuses on the myopathological aspects of primary mitochondrial disorders. The utility of muscle biopsy is not limited to analyse the structural abnormalities; rather it also proves to be a potential tool to understand the deranged sub-cellular functions.
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Affiliation(s)
- Narayanappa Gayathri
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560 029, India.
| | - Sekar Deepha
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560 029, India
| | - Shivani Sharma
- Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 560 029, India
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Finsterer J. Muscle biopsy is not diagnostic for MELAS. J Neurol Sci 2020; 410:116670. [PMID: 31923614 DOI: 10.1016/j.jns.2020.116670] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 01/02/2020] [Indexed: 10/25/2022]
Affiliation(s)
- Josef Finsterer
- Krankenanstalt Rudolfstiftung, Messerli Institute, Vienna, Austria.
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Franco-Iborra S, Tanji K. Histochemical and immunohistochemical staining methods to visualize mitochondrial proteins and activity. Methods Cell Biol 2020; 155:247-270. [PMID: 32183961 DOI: 10.1016/bs.mcb.2019.11.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
We describe here reliable histochemical and immunohistochemical techniques to visualize mitochondria and respiratory chain dysfunction in tissue sections. These morphological methods have been widely used for years, and yet remain relevant to obtain insight into the pathogenesis of mitochondrial diseases. Today, mitochondrial medicine is changing rapidly and genetic information plays an increasing role in the diagnostic process, owing to advances in next-generation sequencing. However, tissue analysis and morphological categorization remain essential, especially when genetic abnormalities of unknown significance might complicate a diagnostic odyssey. Furthermore, tissue assessment is an essential step in laboratory investigation using animal or cell models, in order to assess the distribution, severity, and/or progression of the disease, and to evaluate the effects of possible treatments. Optimized and reproducible staining and imaging methodology are the key elements for accurate tissue assessment. When these methods are used properly and integrated with wisely chosen genetic and biochemical approaches, powerful information can be obtained about the structure and function of mitochondria in both animal model systems and human patients. While the described protocols refer to skeletal muscle and brain mitochondria, the methods described can be applied to any tissue type.
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Affiliation(s)
- Sandra Franco-Iborra
- Department of Pathology and Cell Biology, Columbia University, New York, NY, United States.
| | - Kurenai Tanji
- Department of Pathology and Cell Biology, Columbia University, New York, NY, United States.
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Veiga MGAD, Marecos C, Duarte ST, Vieira JP, Conceição C. Leigh syndrome with atypical cerebellar lesions. eNeurologicalSci 2019; 16:100197. [PMID: 31334367 PMCID: PMC6614543 DOI: 10.1016/j.ensci.2019.100197] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 06/22/2019] [Accepted: 06/26/2019] [Indexed: 11/13/2022] Open
Abstract
Leigh Syndrome is a neurodegenerative disorder caused by mitochondrial dysfunction, with significant phenotypic and genetic heterogeneity. It usually presents in early life, with a severe prognosis. It can be caused by more than 75 different gene mutations, of nuclear and mitochondrial origin, involving all respiratory chain complexes, with less than 25% of Leigh syndrome having mitochondrial DNA mutations. The typical pathologic hallmarks are focal, bilateral, and symmetric lesions in the basal ganglia, thalamus, cerebellum, cerebral white matter and spinal cord gray matter, usually with T2WI and FLAIR hyperintensity. The basal ganglia and thalami frequently present with a pattern of cytotoxic edema. We present one case with clinical and analytical features consistent with Leigh Syndrome, with peculiar imaging features, showing dominant cerebellar edematous changes with unexpected petechial component suggestive of microangiopathy. To our knowledge, these features are unreported and suggest the existence of microvascular lesions. Based on the reported imaging findings, we propose that Leigh Syndrome should be added to the differential diagnosis of acute cerebellitis.
Leigh Syndrome is a neurodegenerative disorder with a severe prognosis. Child with dominant cerebellar findings, with reversible, topographically altering edematous changes, and unexpected petechial component. MRI features previously unreported, representing a new imaging presentation of the syndrome. Suggestion of an unknown microvascular pathophysiologic mechanism eventually related to the process of neurodegeneration. Proposition of Leigh Syndrome addition to the differential diagnosis of acute cerebellitis imaging features in children.
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Affiliation(s)
- Marcos Gil Alberto da Veiga
- Department of Neuroradiology, Centro Hospitalar de Lisboa Central, R. José António Serrano, 1150-199 Lisboa, Portugal
| | - Clara Marecos
- Department of Neuropediatrics, Hospital Dona Estefânia - Centro Hospitalar de Lisboa Central, R. Jacinta Marto, 1169-045 Lisboa, Portugal.,Department of Pediatrics, Hospital Professor Doutor Fernando Fonseca, EPE, IC19, 2720-276 Amadora, Portugal
| | - Sofia Temudo Duarte
- Department of Neuropediatrics, Hospital Dona Estefânia - Centro Hospitalar de Lisboa Central, R. Jacinta Marto, 1169-045 Lisboa, Portugal
| | - José Pedro Vieira
- Department of Neuropediatrics, Hospital Dona Estefânia - Centro Hospitalar de Lisboa Central, R. Jacinta Marto, 1169-045 Lisboa, Portugal
| | - Carla Conceição
- Department of Neuroradiology, Centro Hospitalar de Lisboa Central, R. José António Serrano, 1150-199 Lisboa, Portugal
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Phadke R. Myopathology of Adult and Paediatric Mitochondrial Diseases. J Clin Med 2017; 6:jcm6070064. [PMID: 28677615 PMCID: PMC5532572 DOI: 10.3390/jcm6070064] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2017] [Revised: 06/21/2017] [Accepted: 06/28/2017] [Indexed: 01/09/2023] Open
Abstract
Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA (nDNA) and mitochondrial DNA (mtDNA)) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various omics platforms in unravelling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype–phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field.
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Affiliation(s)
- Rahul Phadke
- Division of Neuropathology, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London WC1N 3BG, UK.
- Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
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Finsterer J, Zarrouk-Mahjoub S. Mitochondrial vasculopathy. World J Cardiol 2016; 8:333-339. [PMID: 27231520 PMCID: PMC4877362 DOI: 10.4330/wjc.v8.i5.333] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2015] [Revised: 01/16/2016] [Accepted: 03/14/2016] [Indexed: 02/06/2023] Open
Abstract
Mitochondrial disorders (MIDs) are usually multisystem disorders (mitochondrial multiorgan disorder syndrome) either on from onset or starting at a point during the disease course. Most frequently affected tissues are those with a high oxygen demand such as the central nervous system, the muscle, endocrine glands, or the myocardium. Recently, it has been shown that rarely also the arteries may be affected (mitochondrial arteriopathy). This review focuses on the type, diagnosis, and treatment of mitochondrial vasculopathy in MID patients. A literature search using appropriate search terms was carried out. Mitochondrial vasculopathy manifests as either microangiopathy or macroangiopathy. Clinical manifestations of mitochondrial microangiopathy include leukoencephalopathy, migraine-like headache, stroke-like episodes, or peripheral retinopathy. Mitochondrial macroangiopathy manifests as atherosclerosis, ectasia of arteries, aneurysm formation, dissection, or spontaneous rupture of arteries. The diagnosis relies on the documentation and confirmation of the mitochondrial metabolic defect or the genetic cause after exclusion of non-MID causes. Treatment is not at variance compared to treatment of vasculopathy due to non-MID causes. Mitochondrial vasculopathy exists and manifests as micro- or macroangiopathy. Diagnosing mitochondrial vasculopathy is crucial since appropriate treatment may prevent from severe complications.
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Suzuki H, Ono M, Kojima Y, Kanda M, Shibasaki H, Oki M, Nakano S. [A case of MELAS associated with histochemical findings of muscles characteristic of MERRF]. Rinsho Shinkeigaku 2016; 56:196-199. [PMID: 26960269 DOI: 10.5692/clinicalneurol.cn-000783] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
We here report a 39-year-old woman of short stature with sensorineural deafness, who suddenly developed status epilepticus. T2-weighed image of brain magnetic resonance imaging (MRI) revealed a high signal lesion in the left temporal area, the distribution of which was not compatible with any particular arterial supply. Lactate and pyruvate were elevated in the serum and cerebrospinal fluid. As the mitochondrial gene analysis revealed the m.3243A>G mutation, diagnosis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) was made. In the histochemical study of a biopsied muscle, the intramuscular blood vessels reacted strongly with SDH (SSV), but the SSV was negative for cytochrome c oxidase (COX), the findings characteristic of myoclonic epilepsy with ragged-red fibers (MERRF). This is the first case of MELAS in which the muscle histochemistry showed positive SSV unassociated with increased COX.
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8
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Lorenzoni PJ, Scola RH, Kay CSK, Silvado CES, Werneck LC. When should MERRF (myoclonus epilepsy associated with ragged-red fibers) be the diagnosis? ARQUIVOS DE NEURO-PSIQUIATRIA 2015; 72:803-11. [PMID: 25337734 DOI: 10.1590/0004-282x20140124] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Accepted: 07/22/2014] [Indexed: 11/22/2022]
Abstract
Myoclonic epilepsy associated with ragged red fibers (MERRF) is a rare mitochondrial disorder. Diagnostic criteria for MERRF include typical manifestations of the disease: myoclonus, generalized epilepsy, cerebellar ataxia and ragged red fibers (RRF) on muscle biopsy. Clinical features of MERRF are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALys gene of the DNAmt, mainly A8344G, are responsible for almost 90% of MERRF cases. Morphological changes seen upon muscle biopsy in MERRF include a substantive proportion of RRF, muscle fibers showing a deficient activity of cytochrome c oxidase (COX) and the presence of vessels with a strong reaction for succinate dehydrogenase and COX deficiency. In this review, we discuss mainly clinical and laboratory manifestations, brain images, electrophysiological patterns, histology and molecular findings as well as some differential diagnoses and treatments.
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Affiliation(s)
- Paulo José Lorenzoni
- Departamento de Neurologia, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil
| | - Rosana Herminia Scola
- Departamento de Neurologia, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil
| | - Cláudia Suemi Kamoi Kay
- Departamento de Neurologia, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil
| | - Carlos Eduardo S Silvado
- Departamento de Neurologia, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil
| | - Lineu Cesar Werneck
- Departamento de Neurologia, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil
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9
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Kirchner S, Ignatova Z. Emerging roles of tRNA in adaptive translation, signalling dynamics and disease. Nat Rev Genet 2014; 16:98-112. [DOI: 10.1038/nrg3861] [Citation(s) in RCA: 355] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Abstract
Mutations in the human mitochondrial genome are known to cause an array of diverse disorders, most of which are maternally inherited, and all of which are associated with defects in oxidative energy metabolism. It is now emerging that somatic mutations in mitochondrial DNA (mtDNA) are also linked to other complex traits, including neurodegenerative diseases, ageing and cancer. Here we discuss insights into the roles of mtDNA mutations in a wide variety of diseases, highlighting the interesting genetic characteristics of the mitochondrial genome and challenges in studying its contribution to pathogenesis.
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Finsterer J, Mahjoub SZ. Primary mitochondrial arteriopathy. Nutr Metab Cardiovasc Dis 2012; 22:393-399. [PMID: 22520486 DOI: 10.1016/j.numecd.2012.01.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Revised: 12/27/2011] [Accepted: 01/05/2012] [Indexed: 12/28/2022]
Abstract
AIM Whether arteries are affected in mitochondrial disorders (MIDs) was under debate for years but meanwhile there are strong indications that large and small arteries are primarily or secondarily affected in MIDs. DATA SYNTHESIS When reviewing the literature for appropriate studies it turned out that vascular involvement in MIDs includes primary or secondary micro- or macroangiopathy of the cerebral, cervical, and retinal arteries, the aorta, the iliac arteries, the brachial arteries, or the muscular arteries. Arteriopathy in MIDs manifests as atherosclerosis, stenosis, occlusion, dissection, ectasia, aneurysm formation, or arteriovenous malformation. Direct evidence for primary cerebral microangiopathy comes from histological studies and indirect evidence from imaging and perfusion studies of the brain. Microangiopathy of the retina is highly prevalent in Leber's hereditary optic neuropathy. Macroangiopathy of the carotid arteries may be complicated by stroke. Arteriopathy of the aorta may result in ectasia, aneurysm formation, or even rupture. Further evidence for arteriopathy in MIDs comes from the frequent association of migraine with MIDs and the occurrence of premature atherosclerosis in MID patients without classical risk factors. CONCLUSIONS Mitochondrial arteriopathy most frequently concerns the cerebral arteries and may result from the underlying metabolic defect or secondary from associated vascular risk factors. Vascular involvement in MIDs has a strong impact on the prognosis and outcome of these patients.
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Affiliation(s)
- J Finsterer
- Danube University Krems, Krems, Postfach 20, 1180 Vienna, Austria.
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Abstract
Oxidative phosphorylation (OXPHOS) accounts for approximately 95% of the adenosine triphosphate (ATP) produced by the cell. The central nervous system, peripheral nervous system, cardiac muscle, skeletal muscle, and smooth muscle are highly susceptible to dysfunction of this complex enzyme system. Although most OXPHOS diseases are multisystem disorders, the neuromuscular manifestations are often prominent and play an important role in patient diagnosis. To assist the neurologist in evaluating these complex patients, this article focuses on selected samples of OXPHOS diseases with identifiable neuromuscular abnormalities and presents an evaluation algorithm to facilitate patient diagnosis.
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Affiliation(s)
- J M Shoffner
- Molecular Medicine Laboratory, Children's Healthcare of Atlanta, GA 30342, USA.
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13
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Abstract
Approximately there years ago, this journal published a review on the clinical and molecular analysis of mitochondrial encephalomyopathies, with emphasis on defects in mitochondrial DNA (mtDNA). At the time, approximately 30 point mutations associated with a variety of maternally-inherited (or rarely, sporadic) disorders had been described. Since that time, almost twenty new pathogenic mtDNA point mutations have been described, and the pace of discovery of such mutations shows no signs of abating. This accumulating body of data has begun to reveal some patterns that may be relevant to pathogenesis.
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Affiliation(s)
- E A Schon
- Department of Neurology, Columbia University, New York, New York 10032, USA
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14
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Abstract
Myoclonic epilepsy with ragged-red fiber syndrome has been associated with a mitochondrial DNA base substitution at nucleotide 8344 in the mitochondrial tRNA(Lys) gene. In several reported series, adult patients with these mutations have mild to moderate symptoms that progress slowly over many years. We describe a girl with MERRF syndrome who had an unusually rapid and severe clinical course, with onset of symptoms at age 7 years and death by age 14 years of overwhelming lactic acidosis. Postmortem tissue biopsy revealed variable but generally high percentages of mutant mitochondrial genomes in multiple organ systems. Twenty-one other members of her family were tested for the mutation and had varying percentages in leukocytes.
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Affiliation(s)
- T D Sanger
- Department of Pediatrics, USC + Los Angeles County Medical Center, USA
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Ozawa M, Goto Y, Sakuta R, Tanno Y, Tsuji S, Nonaka I. The 8,344 mutation in mitochondrial DNA: a comparison between the proportion of mutant DNA and clinico-pathologic findings. Neuromuscul Disord 1995; 5:483-8. [PMID: 8580730 DOI: 10.1016/0960-8966(95)00009-c] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Ten patients, two men and eight women with mitochondrial encephalomyopathy, had an A-G mutation at nucleotide pair 8,344 in the mitochondrial DNA, the most common genetic defect in myoclonus epilepsy with ragged-red fibers (MERRF). Eight patients had the clinical and pathologic characteristics of MERRF including myoclonus, seizures, cerebellar ataxia and myopathy with ragged-red fibers. Two patients had atypical symptoms such as early onset of fatal cardiac failure and late onset of rapid mental deterioration, respectively. The striking feature in our patients with the 8,344 mutation cardiac involvement and two developed progressive heart failure. In the typical MERRF patients, the proportion of mutant mitochondrial DNA in their skeletal muscles, quantified by a single strand conformation polymorphism analysis, was above 85%. However, there was no significant correlation between clinical severity, histopathological findings and the proportion of mutant mtDNA in muscle biopsy samples, suggesting that non-ragged-red fibers play an important role in the phenotype expression of the mutants.
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Affiliation(s)
- M Ozawa
- Department of Laboratory Medicine, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
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16
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Abstract
MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes) is a distinct disorder characterized clinically by repeated strokelike attacks mostly beginning in childhood. We have paid special attention to the blood vessel abnormality seen in most biopsied muscle, in terms of the strokelike episodes in MELAS. The 3243 mutation in 80% of the typical MELAS patients has also been found in patients differing from the MELAS phenotype. Because we have examined muscle biopsies in 94 MELAS or 3243-positive patients, it is worthwhile to summarize the clinical and pathological findings and to prove the discrepancy between phenotype and genotype. This may be a starting point for further discussion of the pathomechanism and so toward further understanding of the disease itself.
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Affiliation(s)
- Y Goto
- Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan
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Kumode M, Yamano T, Shimada M. Histochemical study of mitochondrial enzymes in cerebellar cortex of macular mutant mouse, a model of Menkes kinky hair disease. Acta Neuropathol 1994; 87:313-6. [PMID: 8009964 DOI: 10.1007/bf00296748] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The cerebellar Purkinje cells in the hemizygote of the macular mutant mouse contain numerous abnormal mitochondria which show a marked decrease in cytochrome c oxidase activity. Using histochemical methods we studied the activity of other mitochondrial enzymes, such as NADH diaphorase and succinic dehydrogenase, in the cerebellar cortex of this mutant mouse. Such activities were markedly increased in the Purkinje cells, especially in the soma and stem dendrite, from 10 days after birth in the hemizygote as compared with findings in normal littermates. These results were considered to be due to an increased number of abnormal mitochondria.
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Affiliation(s)
- M Kumode
- Department of Pediatrics, Shiga University of Medical Science, Japan
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Coquet M, Degoul F, Vital A, Malgat M, Mazat JP, Louvet-Giendaj C, Fontan D, Tison F, Diry M, Marsac C. Merrf family with 8344 mutation in tRNA (lys). Evidence of a mitochondrial vasculopathy in muscle biopsies. Neuromuscul Disord 1993; 3:593-7. [PMID: 8186718 DOI: 10.1016/0960-8966(93)90122-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
This article reports a new MERRF family. The mother, regarded as suffering from Ramsay-Hunt Syndrome, and her three daughters, had the same clinical pattern: myoclonic epilepsy and ataxia. Two daughters were studied on morphological, biochemical and molecular genetic levels. Muscle biopsies showed ragged-red fibres and mitochondrial vasculopathy. Arterioles were strongly SDH-reactive and COX-negative. By electron microscopy, abnormal mitochondria were observed in skeletal muscle fibres, in smooth muscle fibres of intramuscular vessels and in sweat gland epithelium. The study of the respiratory chain showed complex IV and I + IV deficiency, respectively. Mitochondrial tRNA (lys) mutation at position 8344 was pointed out as previously reported in the MERRF syndrome.
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Affiliation(s)
- M Coquet
- Department of Neuropathology, CHU Bordeaux, France
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