1/46. adult-onset MELAS presenting as herpes encephalitis.OBJECTIVE: To report an unusual presentation of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) manifested in late life with a clinical picture of herpes simplex encephalitis. DESIGN: Case report. SETTING: Clinical neurology department in a tertiary care hospital. CASE DESCRIPTION: A 55-year-old woman developed aphasia and delirium during ophthalmic herpes zoster infection treated with oral prednisone and ophthalmic steroids, which was followed by progressive cognitive decline without acute neurologic events for 5 years. At age 60, the patient presented with new onset of seizures, hemiparesis, and hemianopsia. Subsequently she developed cortical blindness, multiple traumatic soft tissue injuries from falls, acute psychosis, and severe dementia with periods of agitation. She died in a nursing home in March 1997, 6 years after initial presentation. RESULTS: magnetic resonance imaging scan of the brain showed hyperintensity on T2-weighted images involving temporal, parietal, and occipital lobes bilaterally as well as mild atrophy of brainstem and cerebellum. Single photon emission computed tomographic imaging showed hypoperfusion of temporal, parietal, and occipital lobes. Results of video electroencephalographic monitoring showed periodic lateralizing epileptiform discharges in temporal and occipital areas. The serum lactate level was normal in May 1996 and elevated in October 1996. The creatine kinase level was elevated with a 100% MM fraction in August 1991 and normal in March 1996. Results of repeated cerebrospinal fluid analyses indicated elevated protein levels. Analysis of dna was diagnostic of MELAS by mitochondrial dna point mutation at position 3243. The results of autopsy showed moderate cerebral, cerebellar, and brainstem atrophy with signs of infarction in temporal and parietal lobes bilaterally. CONCLUSIONS: The clinical presentation as well as age at onset of MELAS are highly variable. Onset of mitochondrial disorders can be provoked by febrile illness when there is mismatch between energy requirements and availability. In the differential diagnosis of herpes encephalitides, melas syndrome should be considered.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
2/46. Tissue mosaicism in the skeletal muscle and sural nerve biopsies in the melas syndrome.We describe a clinically full-blown MELAS patient, who had an A3243G point mutation of mitochondrial dna (mtDNA) in muscle and blood cells, and his family members. From the proband two muscle biopsies from the vastus lateralis muscle were analysed; one had typical ragged red fibers and focal cytochrome c oxidase deficiency and the other was completely normal. He also had a peripheral neuropathy confirmed by nerve conduction velocity and sural nerve biopsy studies. Axonal degeneration, relative loss of large myelinated fibers and paracrystalline inclusion bodies in the schwann cells were noted. Intriguingly, the A3243G mutation of mtDNA was not found in the sural nerve biopsy. Therefore, we conclude that tissue mosaicism is present in the muscle fibers and that the mtDNA mutation may not be detected in the nerve involved as proved by pathology. We also suggest that the involvement of specific tissues in patients with mitochondrial diseases should be further determined by single fiber mtDNA analysis.- - - - - - - - - - ranking = 2826.8765509059keywords = family, family member, member (Clic here for more details about this article) |
3/46. MELAS with prominent white matter gliosis and atrophy of the cerebellar granular layer: a clinical, genetic, and pathological study.This report concerns an autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with unusual neuropathological findings. The patient was a Japanese woman who was 21 years old at the time of death. Her mother is a patient with genetically confirmed MELAS. Her clinical manifestations included convulsions and lactic acidosis in the latter half of the first decade of life, followed by deafness, dementia, muscle weakness in the lower extremities, slight ataxia in the upper and lower extremities, and diabetes mellitus. Muscle biopsy revealed ragged-red fibers, and genetic study showed a point mutation at nucleotide pair 3243 in mitochondrial dna. She died of lactic acidosis. In the clinical course, she did not develop stroke-like episodes. The neuropathological examination revealed not only minute to small necrotic foci in the cerebral cortex, amygdala, hippocampus, and cerebellum, but also prominent white matter gliosis in the central nervous system and cerebellar cortical degeneration of granular cell type. Our neuropathological findings, including prominent white matter gliosis of the central nervous system and cerebellar cortical degeneration of granular cell type, may indicate morphologically widespread cellular dysfunction, not restricted to either neuronal or vascular derangement, in the brain pathology of MELAS.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
4/46. Mitochondrial maculopathy: geographic atrophy of the macula in the MELAS associated A to G 3243 mitochondrial dna point mutation.PURPOSE: To report ocular findings in the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (melas syndrome) in a family with the A to G 3243 mitochondrial (mt) dna point mutation. methods: case reports. Ocular findings are described from four family members with the MELAS associated A to G 3243 mt dna point mutation. RESULTS: Findings included ophthalmoplegia, neurosensory deafness, reduction of photopic and scotopic electroretinogram b-wave amplitudes, and myopathy, as well as macular retinal pigment epithelial atrophy. No family members had nyctalopia, attenuation of retinal blood vessels, or retinal bone spicule pigmentation. CONCLUSION: The finding of slowly progressive macular retinal pigment epithelial atrophy expands the reported phenotypic diversity of patients with A3243G mt dna mutations.- - - - - - - - - - ranking = 7961.1983349756keywords = family, family member, member (Clic here for more details about this article) |
5/46. Phenotypic heterogeneity in a Chinese family with mitochondrial disease and A3243G mutation of mitochondrial dna.The A3243G mutation of mitochondrial dna (mtDNA) has been shown to be responsible for or associated with mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes (MELAS) syndrome, diabetes mellitus (DM) and several other neuromuscular diseases. We used polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) to identify the A3243G mtDNA mutation and an electron microscope to examine mitochondrial derangement in the muscle biopsies of a 38-year-old man suspected to have melas syndrome with DM. We found great variability in the clinical presentation and in the proportion of mtDNA with the A3243G mutation in the matrilineal family members of the patient. The proband had atypical melas syndrome, recurrent vascular headache, and DM (MELASDM), and his mother manifested chronic progressive ptosis and DM (CPPDM). brain magnetic resonance imaging of the proband showed high signal intensity in the left temporoparieto-occipital area on T2 weighted images (T2WI). The blood lactate level ranged from 2.32 to 4.70 mmol/l, and two-hour postprandial glucose ranged from 124 mg/dl to 148 mg/dl. The blood lactate and postprandial glucose of the proband's mother were 3.15 mmol/l and 192 mg/dl, respectively. Electron microscopic examination of a muscle biopsy of the patient showed abnormal mitochondria with decreased density of cristae and membrane degeneration. No ragged-red fibers were detected in muscle upon staining with modified Gomori trichrome. The hair follicles and blood cells of the patient and his mother showed the A3243G mutation in the tRNA(Leu)(UUR) gene. The proportions of the mutant dna in the hair follicles and blood cells of the proband were 36.8% and 35.2%, respectively, and those of the patient's mother were 28.8% and 13.9%, respectively. We conclude that the A3243G mtDNA mutation may manifest with MELASDM or CPPDM in different matrilineal members of the same family as a result of differences in random segregation of the heteroplasmic A3243G mutant mtDNA in the affected tissues of patients.- - - - - - - - - - ranking = 14428.677994731keywords = family, family member, member (Clic here for more details about this article) |
6/46. Neuromuscular syndrome associated with the 3291T-->C mutation of mitochondrial dna: a second case.A mutation was found in an Italian child affecting the gene encoding the mitochondrial transfer rna for leucine (codon UUR). This mutation (3291T-->C) had previously been reported in a single Japanese patient. In contrast with the original patient, who suffered from early-onset mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), our patient presented an apparently isolated mild myopathy. Mutational analysis in the proband and her family showed that the mutation was heteroplasmic, and that its relative amount was positively correlated with the severity of the phenotype. These findings lead to the definitive confirmation that the 3291T-->C is indeed pathogenic. As commonly found in mitochondrial-dna related disorders, also for this mutation different clinical manifestations can be associated with the same genetic abnormality.- - - - - - - - - - ranking = 2307.4452331637keywords = family (Clic here for more details about this article) |
7/46. De novo mutation in the mitochondrial tRNALeu(UUR) gene (A3243G) with rapid segregation resulting in MELAS in the offspring.A 14-year-old Chinese boy with a normal perinatal and early developmental history presented at 5 years of age with migraine, intractable epilepsy, ataxia, supraventricular tachycardia, paralytic ileus and progressive mental deterioration. Computerized tomography revealed multiple cerebral infarcts in the parieto-occipital region without basal ganglial calcification. magnetic resonance imaging showed increased signal intensity in T2 weighted images in the same regions. A cerebral digital subtraction angiogram was normal. Venous lactate, pyruvate, lactate to pyruvate ratio and cerebrospinal fluid lactate were elevated. Muscle biopsy did not reveal any ragged red fibres; dinucleotide-tetrazolium reductase activity was normal. Mitochondrial dna analysis detected an adenine to guanine mutation at nucleotide position 3243 of tRNALeu(UUR). All four tissues analysed demonstrated heteroplasmy: leucocyte 56%, hair follicle 70%; buccal cell 64%; muscle 54%. The mother and brother of the proband, both asymptomatic, were also found to have a heteroplasmic A3243G mutation in the leucocytes, hair follicle and buccal cells. Other members of the maternal lineage, including the maternal grandmother, did not have the mutation. This report describes a patient with mitochondrial encephalopathy, lactic acidosis, stroke-like episodes, who presented with multisystem involvement. The absence of ragged red fibres in muscle biopsy did not preclude the diagnosis. Mutational analysis of mitochondrial dna conveniently confirmed the diagnosis of the disorder. A de novo mutation is demonstrated in this family.- - - - - - - - - - ranking = 2372.0205111705keywords = family, member (Clic here for more details about this article) |
8/46. mtDNA disease in the primary care setting.Disorders of mitochondrial dna (mtDNA) may commonly present to primary care physicians but go undiagnosed. A 36-year-old man with a 15-year history of psychosis, seizures, and sensorineural hearing loss and a family history of diabetes mellitus and heart disease presented to our hospital without a unifying diagnosis. Physiologic, biochemical, and genetic testing revealed deficient aerobic metabolism, a defect in mitochondrial electron transport, and the presence of an A-to-G point mutation at position 3243 of the mitochondrial leucine-transfer rna gene, establishing the diagnosis of mitochondrial encephalopathy, lactic acidosis, and strokelike syndrome (MELAS). Diagnosing mtDNA disorders requires a careful integration of clinical signs and symptoms with pedigree analysis and multidisciplinary testing. diagnosis is important to provide genetic counseling, avoid unnecessary evaluation, and facilitate therapy for symptomatic relief.- - - - - - - - - - ranking = 2307.4452331637keywords = family (Clic here for more details about this article) |
9/46. Detection of dna mutations associated with mitochondrial diseases by Agilent 2100 bioanalyzer.BACKGROUND: Molecular analysis of mitochondrial dna (mtDNA) has provided a final diagnosis for many of the mitochondrial diseases. We evaluated the Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, CA) to determine whether the system could replace the conventional restriction fragment length polymorphism (RFLP) analysis by the agarose gel electrophoresis for the detection of the mtDNA mutation. methods: Three members of a family with melas syndrome and four members of a family with merrf syndrome were recruited for this study. After PCR and restriction enzyme digestion, dna fragments were separated on the Agilent 2100 bioanalyzer in conjunction with the dna 500 and dna 1000 Labchip kits and by electrophoresis on precast 3% agarose gels. RESULTS: The data generated by the dna 500 and dna 1000 assays using the Agilent 2100 bioanalyzer showed a lower percentage error and a better reproducibility as compared to those obtained by the conventional method. CONCLUSION: Based on the performance of the bioanalyzer, we suggest that this novel Labchip is adequate to replace the current RFLP analysis by the agarose gel electrophoresis for mtDNA mutation detection.- - - - - - - - - - ranking = 4744.0410223411keywords = family, member (Clic here for more details about this article) |
10/46. intestinal pseudo-obstruction and urinary retention: cardinal features of a mitochondrial dna-related disease.The syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystemic disorder associated in most of the patients with an A to G transition at nucleotide position 3243 in the transfer rna (tRNA)Leu(UUR) (A3243G) of the mitochondrial dna. This syndrome is characterized by the preponderant involvement of skeletal muscle and central nervous system, but urinary or gastrointestinal symptoms are seldom documented. Here we report an unusual case of a 52-year-old woman with a clinical phenotype characterized by encephalopathy, left hemiparesis, urinary retention and gastrointestinal pseudo-obstruction. She had the classical A3243G mitochondrial dna point mutation of melas syndrome. We also present a clinically heterogeneous multigenerational pedigree with several affected members in the maternal lineage.- - - - - - - - - - ranking = 64.575278006797keywords = member (Clic here for more details about this article) |
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