Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0162671 (MELAS)
 587 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Defects in mitochondrial DNA (mtDNA) are associated with several different human diseases, including the mitochondrial encephalomyopathies. The mutations include deletions but also duplications and point mutations. Individuals with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) carry a common A-to-G substitution in a highly conserved portion of the gene for transfer RNA(Leu(UUR)). Although the MELAS mutation may be comparable to the defect in the tRNA(Lys) gene associated with MERRF (myoclonus epilepsy associated with ragged-red fibres), it is also embedded in the middle of a tridecamer sequence necessary for the formation of the 3' ends of 16S ribosomal RNA in vitro. We found that the MELAS mutation results in severe impairment of 16S rRNA transcription termination, which correlates with a reduced affinity of the partially purified termination protein for the MELAS template. This suggests that the molecular defect in MELAS is the inability to produce the correct type and quantity of rRNA relative to other mitochondrial gene products.
 ...
PMID:Impairment of mitochondrial transcription termination by a point mutation associated with the MELAS subgroup of mitochondrial encephalomyopathies. 175 69

During a 4-year period 1984 to 1988, 20 children referred with manifestations of central nervous system or neuromuscular disease combined with hyperlactatemia were found to have a mitochondrial disease. Each diagnosis was based on the results of thorough biochemical and morphologic investigations. The patients were separated into one series with mainly encephalopathy (n = 14) and another with mainly myopathy (n = 6). The patients with encephalopathy had the following syndromes: Kearns-Sayre (n = 2), MERRF (myoclonus epilepsy and ragged red fibers; n = 2), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes; n = 3), Alpers (n = 3), Leigh (n = 1), and other variants (n = 3). In patients with myopathy, three had hypertrophic nonobstructive cardiomyopathy. Ultrastructural abnormalities of mitochondria were the most common morphologic changes in the muscle biopsies. Complex I deficiency was most common in the patients with encephalopathy. All of the patients with myopathy had complex IV deficiency. Mutations of mitochondrial DNA were found in six patients with encephalopathy. We conclude that identification of defects at the DNA level and determination of the phenotypic expression with clinical, morphologic, and biochemical methods are fundamental for future rational classification of mitochondrial disorders.
 ...
PMID:Mitochondrial encephalomyopathies in childhood. II. Clinical manifestations and syndromes. 186 Dec 10

EEG was studied in 25 children and adolescents with mitochondrial encephalomyopathies, defined on the basis of clinical, biochemical and morphological criteria. Twenty cases conformed to well-known mitochondrial syndromes: Alpers syndrome [6], Leigh syndrome [2], MERRF (myoclonus epilepsy and ragged red fibers) syndrome [3], MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) syndrome [5] and Kearns-Sayre syndrome [4]. Many patients were followed for several years with repeated EEG. In all, 112 EEG records were included in the study. A common feature of all the mitochondrial encephalomyopathic syndromes was slowing of the alpha rhythm. Epileptic discharges were seen in most syndromes. In spite of the small number of cases in each group, in Alpers, MERRF and MELAS syndromes we found sequential EEG patterns which seemed to be typical of the respective syndromes. In contrast, in Kearns-Sayre syndrome, a slow background rhythm was the only consistent finding. We conclude that EEG, especially repeated recordings, may be of help in the diagnostic evaluation of mitochondrial encephalomyopathies.
 ...
PMID:EEG findings in children and adolescents with mitochondrial encephalomyopathies: a study of 25 cases. 192 9

Myoclonus epilepsy associated with ragged-red fibers (MERRF) is a degenerative disease involving dentate nuclei of the cerebellum, globus pallidus, the posterior columns and spinocerebellar tracts of the spinal cord, and skeletal muscles. Abnormal mitochondria were observed in the cells of the cerebellar cortex and of the dentate nuclei. The main symptoms of this disease include cerebellar ataxia and myoclonus in addition to muscular wasting. Patients with MELAS occasionally have myoclonus, but they never have myoclonus as their initial symptoms. Most of the patients with both clinical features of MERRF and MELAS were regarded as belonging to the category of MELAS.
 ...
PMID:MERRF: a clinicopathological study. Relationships between myoclonus epilepsies and mitochondrial myopathies. 196 54

The last two decades have revealed a novel group of inborn errors with defects on the pathways of aerobic energy substrates into the mitochondria or the capacity to generate reducing potential from these substrates, as well as those that block the oxidative phosphorylation pathway itself. The mitochondrial diseases are clinically heterogenous disorders that can affect multiple organ systems, mainly the skeletal muscle and nervous system (mitochondrial encephalomyopathies). There are a few distinctive syndromes such as Leigh's syndrome, Alper's syndrome, Kearns-Sayre's syndrome, myoclonus epilepsy with "ragged-red fibres" (MERRF), and MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, strokelike episodes). The last year our department has evaluated ten children with mitochondrial disorders. Among these are two siblings with Leigh's syndrome and cytochrome c-oxidase defect. The first child, a girl, developed the first symptoms at the age of four months and died 13 months old. The younger brother showed the same clinical picture as his sister. However, the clinical neurological picture was stabilized when he was 18 months old, and he is still alive at six years of age and slightly psychomotorically retarded.
 ...
PMID:[Mitochondrial diseases--more common than we realize?]. 199 73

Severe prolonged migrainous symptoms and prolonged partial status epilepticus are characteristic features of the MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Maternal transmission previously found in myoclonus epilepsy and ragged-red fibers (MERRF), another mitochondrial disease, is suggested in this disorder as well.
 ...
PMID:MELAS syndrome: characteristic migrainous and epileptic features and maternal transmission. 336 73

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.
 ...
PMID:Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies. 825 44

The mitochondrion is the only extranuclear organelle containing DNA (mtDNA). As such, genetically determined mitochondrial diseases may result from a molecular defect involving the mitochondrial or the nuclear genome. The first is characterized by maternal inheritance and the second by Mendelian inheritance. Ragged-red fibers (RRF) are commonly seen with primary lesions of mtDNA, but this association is not invariant. Conversely, RRF are seldom associated with primary lesions of nuclear DNA. Large-scale rearrangements (deletions and insertions) and point mutations of mtDNA are commonly associated with RRF and lactic acidosis, e.g. Kearns-Sayre syndrome (KSS) (major large-scale rearrangements), Pearson syndrome (large-scale rearrangements), myoclonus epilepsy with RRF (MERRF) (point mutation affecting tRNA(lys) gene), mitochondrial myopathy, lactic acidosis, and stroke-like episodes (MELAS) (two point mutations affecting tRNA(leu)(UUR) gene) and a maternally-inherited myopathy with cardiac involvement (MIMyCa) (point mutation affecting tRNA(leu)(UUR) gene). However, RRF and lactic acidosis are absent in Leber hereditary optic neuropathy (LHON) (one point mutation affecting ND4 gene, two point mutations affecting ND1 gene, and one point mutation affecting the apocytochrome b subunit of complex III), and the condition associated with maternally inherited sensory neuropathy (N), ataxia (A), retinitis pigmentosa (RP), developmental delay, dementia, seizures, and limb weakness (NARP) (point mutation affecting ATPase subunit 6 gene). The point mutations in MELAS, MIMyCa, and MERRF, and the large-scale mtDNA rearrangements in KSS and Pearson syndrome have a broader biochemical impact since these molecular defects involve the translational sequence of mitochondrial protein synthesis. The nuclear defects involving mitochondrial function generally are not associated with RRF. The biochemical classification of mitochondrial diseases principally catalogues these nuclear defects. This classification divides mitochondrial diseases into five categories. Primary and secondary deficiencies of carnitine are examples of a substrate transport defect. A lipid storage myopathy is often present. Disturbances of pyruvate or fatty acid metabolism are examples of substrate utilization defects. Only four defects of the Krebs cycle are known: fumarase deficiency, dihydrolipoyl dehydrogenase deficiency, alpha-ketoglutarate dehydrogenase deficiency, and combined defects of muscle succinate dehydrogenase and aconitase. Luft disease is the singular example of a defect in oxidation-phosphorylation coupling. Defects of respiratory chain function are manifold. Two clinical syndromes predominate, one involving limb weakness, and the other primarily affecting brain function. Leigh syndrome may result from different enzyme defects, most notably pyruvate dehydrogenase complex deficiency, cytochrome c oxidase deficiency, complex I deficiency, and complex V deficiency associated with the recently described NARP point mutation. A new group of mitochondrial diseases has emerged.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The expanding clinical spectrum of mitochondrial diseases. 833 7

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.
 ...
PMID:Overlapping syndrome of MERRF and MELAS: molecular and neuroradiological studies. 835 81

Myoclonic seizures, intractable abdominal pain, and headaches resolved during the concomitant administration of sodium dichloroacetate and vita min B1 in two Japanese siblings with the MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike syndrome).
 ...
PMID:Concomitant administration of sodium dichloroacetate and vitamin B1 for lactic acidemia in children with MELAS syndrome. 932 26


1 2 Next >>