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Query: UMLS:C0162671 (MELAS)
 587 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial Encephalomyopathies are primary disorders of energy metabolism recently described. They are the result of mitochondrial abnormalities with a wide spectrum of syndromes implying a multisystemic but predominantly muscular and cerebral involvement. Biochemical, histological, imagiologic and clinical features of the three well known mitochondrial syndromes (MERRF, MELAS and KSS) are described, as well as the mitochondrial genetics and maternal inheritance pattern.
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PMID:[Mitochondrial encephalomyopathies]. 794 40

Mitochondrial diseases are heterogeneous and characterized by a primary defect of the mitochondrial energy output. Genetic defects of mitochondrial energy enzymes may be due to either nuclear DNA gene mutations or mitochondrial DNA (mtDNA) mutations. Among hereditary defects of nuclear-encoded mitochondrial enzymes, carnitine palmitoyltransferase II (CPT-II) deficiency and pyruvate dehydrogenase complex (PDHC) deficiency are of major interest to the neurologist. Several mutations in the CPT-II gene as well as in the X-linked E1 alpha subunit gene of PDHC have been reported and associated with different clinical phenotypes. mtDNA-related syndromes include mitochondrial encephalomyopathies (e.g. MELAS, MERRF, NARP, MIMyCa, etc.), 'pure' encephalopathies (e.g. LHON) and a few syndromes involving only non-neurological systems (e.g. Pearson's pancreas-bone marrow syndrome or diabetes mellitus). Three kinds of molecular lesions have been identified in mtDNA-related disorders: point mutations of protein-encoding mtDNA genes (mit- mutations), point mutations of mtDNA-tRNA genes (syn- mutations) and large-scale rearrangements of mtDNA (rho- mutations). Point mutations (mit- and syn+) are usually maternally inherited, while single large-scale mtDNA rearrangements are usually sporadic. Furthermore, mendelian traits leading to either qualitative or quantitative abnormalities of mtDNA (i.e. multiple mtDNA deletions and tissue-specific mtDNA depletion, respectively) are the first examples of genetic dysfunction of nuclear-mitochondrial communication. In most cases, the molecular detection of the known defects of mtDNA can be carried out by non-invasive techniques, thus making it an easy and relatively inexpensive procedure in the differential diagnosis of the mitochondrial disorders, a rapidly expanding area of clinical neurology.
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PMID:Mitochondrial diseases. 795 50

We studied free radical, lipid peroxide (LPO) and antioxidant levels of blood in three cases with mitochondrial encephalomyopathy. Case 1 was a 17-year-old man with MELAS. Serum vitamin E levels were decreased and LPO levels were increased after stroke-like episodes in case 1. Case 2 was a 68-year-old woman with MELAS and a maternal elder aunt of case 1. She showed an elevated serum LPO levels (6.58 nmol/ml) in the absence of stroke-like episode and serum CoQ10 level was 0.54 microgram/ml before therapy. By CoQ10, idebenone and tocopherol nicotinate therapy, serum LPO levels decreased gradually in parallel with the decrease of lactate and pyruvate levels. Free radicals were measured in case 2 and controls by spin trapping method. Hydroxyl radical and C center radical were increased and H radical was normal in blood. But these free radicals in serum were all normal. Her serum antioxidants revealed an elevated percent inhibition of SOD and a decreased transfferin level. Case 3 was a 52-year-old woman with MERRF. She showed an elevation of serum LPO (12.8 nmol/ml). Her serum antioxidants revealed an elevated vitamin E and ceruloplasmin levels and percent inhibition of SOD.
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PMID:[Free radical, lipid peroxide and antioxidant in mitochondrial encephalomyopathy]. 795 20

In two sibs antenatal ultrasonography revealed identical intracranial calcification, ventricular widening and microcephaly. The first pregnancy was artificially terminated at 19 weeks. Post-mortem examination of the brain revealed destructive calcification and extracerebral neuronal heterotopia. The second sib went to term but died 48 h after birth from irreversible lactic acidosis. Autopsy showed extensive encephalopathy with cavitation and calcification in the cerebral hemispheres, polymicrogyria, multiple neuronal heterotopia, partial callosal dysgenesis, and severe Leigh syndrome, together forming a continuum of early and late brain disruption. Mitochondrial respiratory chain abnormalities, mainly affecting complexes I and IV, and deficiency of pyruvate dehydrogenase complex were detected in skeletal muscle and in liver. A normal functioning of the respiratory chain was found in the fibroblasts. Analysis of mtDNA from muscle, liver and blood revealed normal amounts of intact mtDNA without any of the known point mutations associated with MELAS, MERRF or Leigh syndromes. The early fetal disruption and necrotic changes in the brains of sibs indicate a specific genetically determined disorder which affects neuronal migration, a finding not previously associated with respiratory chain disorders. The present disorder may mimic antenatal congenital infectious encephalopathy because of the combined finding of microcephaly and destructive intracerebral calcification.
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PMID:Familial mitochondrial encephalopathy with fetal ultrasonographic ventriculomegaly and intracerebral calcifications. 795 69

In recent years, several point mutations in the mitochondrial genome have been associated with human disease. PCR Polymerase Chain Reaction/restriction endonuclease based techniques provide a reliable method for screening large numbers of specimens for many of the reported mutations. Muscle tissue usually carries the mutations and has been used in earlier studies. We describe a technique for analysis of mtDNA derived from hair follicles for a range of mutations. Both the 3243 A-->G MELAS and 8344 A-->G MERRF mutations were detected in mtDNA from hair follicles. In patients where both muscle and hair were screened, the mutation load was apparently higher in muscle. Furthermore, in patients positive for a given mutation, all the hair follicles analysed were shown to harbour the mutation, although the proportion of wild type to mutant mtDNA was found to somewhat vary. The advantages of this method are (1: six hair follicles provide sufficient mtDNA for analysis of at least 20 different mutations, and (2: specimen collection and transport to a central laboratory are easier than for other tissues. Our studies show that hair follicles constitute a reliable specimen for mitochondrial mutation screening at a diagnostic level.
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PMID:Rapid and noninvasive screening of patients with mitochondrial myopathy. 798 17

We review the main features of human mitochondrial function and structure, and in particular mitochondrial transcription, translation, and replication cycles. Furthermore, some pecularities such as mitochondria's high polymorphism, the existence of mitochondrial pseudogenes, and the various considerations to take into account when studying mitochondrial diseases will also be mentioned. Mitochondrial syndromes mostly affecting the nervous system have, during the past few years, been associated with mitochondrial DNA (mt DNA) alterations such as deletions, duplications, mutations and depletions. We suggest a possible classification of mitochondrial diseases according to the kind of mt DNA mutations: structural mitochondrial gene mutation as in LHON (Leber's Hereditary Optic Neuropathy) and NARP (Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa) as well as some cases of Leigh's syndrome; transfer RNA and ribosomal RNA mitochondrial gene mutation as in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike Episodes) or MERRF (Myoclonic Epilepsy with Ragged Red Fibers) or deafness with aminoglycoside; structural with transfer RNA mitochondrial gene mutations as observed in large-scale deletions or duplications in Kearns-Sayre syndrome, Pearson's syndrome, diabetes mellitus with deafness, and CPEO (Chronic Progressive External Ophtalmoplegia). Depletions of the mt DNA may also be classified in this category. Even though mutations are generally maternally inherited, most of the deletions are sporadic. However, multiple deletions or depletions may be transmitted in a mendelan trait which suggests that nuclear gene products play a primary role in these processes. The relationship between a mutation and a particular phenotype is far from being fully understood. Gene dosage and energic threshold, which are tissue-specific, appear to be the best indicators. However, the recessive or dominant behavior of both the wild type or the mutated genome appears to play a significant role, which can be verified with in vitro studies.
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PMID:Mitochondrial DNA alterations and genetic diseases: a review. 799 80

Alterations of the mitochondrial DNA, encoding important parts of the cellular energy-generating system (oxidative phosphorylation, OXPHOS), are often associated with the occurrence of degenerative neuromuscular diseases. Especially point mutations in the mitochondrial tRNA genes, which cannot be complemented by the nuclear encoded tRNAs, are candidates for severe defects of the OXPHOS system. An A to G transition at nt 8344 in the tRNA(Lys) gene has been associated with MERRF disease whereas an A to G substitution at nt 3243 in the tRNA(Leu) gene has been linked to the MELAS syndrome. These two mtDNA alterations as well as point mutations in protein-coding genes can be detected simultaneously by an allele-specific amplification of the altered mtDNA. This assay allows the reliable detection of heteroplasmic point-mutations, even if the mutated DNA appears to a small extent of less than 1%.
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PMID:A rapid and sensitive PCR screening method for point mutations associated with mitochondrial encephalomyopathies. 817 30

Localized brain proton MR spectra were acquired from patients with different mitochondrial encephalomyopathies (myoclonus epilepsy with ragged-red fibers [MERRF], Kearns-Sayre syndrome [KSS], and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS]). The regional brain metabolic abnormalities in patients with these syndromes showed different features consistent with the distinct phenotypes. 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. There were significant decreases in N-acetylaspartate/creatine (a measure of neuronal loss or dysfunction) in central cerebral volumes of demented patients and, more prominently, in occipital volumes. In the one patient in whom it was studied, the cerebellum also showed a decreased N-acetylaspartate/creatine. Spectra from two patients with KSS both showed large (four- to sevenfold) increases in lactate/creatine and large decreases in N-acetylaspartate/creatine in central brain volumes. 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. Serial studies emphasized that the regional metabolic abnormalities in MELAS are highly variable as the stroke-like lesions appear and evolve.
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PMID:Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies. 825 44

We describe a 42-year-old woman with overlapping syndrome of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonus epilepsy and ragged-red fibers). Clinically, she had episodic headache, stroke-like episode with left hemiparesis and lactic acidosis commonly found in MELAS syndrome. However, myoclonus seizure, and ataxia with dyssynergic gait characteristic of MERRF were also noted. Computed tomographic scans showed a right temporo-parietal hypodense lesion. The lesion disappeared 20 months later, even magnetic resonance images also failed to reveal this abnormality. A molecular analysis of mitochondrial DNA was conducted by using restriction endonucleases ApaI and NaeI. A transition from A to G was found at the nucleotide position 3243, but not found at the 8344th nucleotide pair. In this report, we document the fluctuating CT changes and emphasize the importance of molecular analysis in patients with overlapping syndrome of mitochondrial encephalomyopathies.
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PMID:Overlapping syndrome of MERRF and MELAS: molecular and neuroradiological studies. 835 81

Recent advances in molecular genetics have led to a better understanding of mitochondrially inherited diseases. Mitochondrial encephalomyopathy overlap syndrome is one such group of diseases in which ocular abnormalities are frequently manifest. The authors describe the clinical, molecular genetic, and pathologic findings of two patients with the mitochondrial encephalomyopathy overlap syndrome. The patients shared a similar clinical course with features overlapping the three traditionally distinct clinical phenotypes (the Kearns-Sayre syndrome; the syndrome of mitochondrial encephalopathy, lactic acidosis, and stroke [MELAS], and the syndrome of myoclonus, epilepsy, and ragged red fibers [MERRF]). The patients had identical mitochondrial DNA mutations (at nucleotide position 3243) and had similar ultrastructural abnormalities, including abundant enlarged mitochondria with "whorled" and "tubular" cristae. These abnormal mitochondria appeared to be preferentially distributed in cells with high metabolic activity (retinal pigment epithelium, corneal endothelium, and extraocular muscles).
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PMID:Ocular clinicopathologic study of the mitochondrial encephalomyopathy overlap syndromes. 836 69


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