Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines the relationship of genotype to phenotype in 14 unselected patients who were found to harbour the A3243G transition in the mitochondrial transfer RNALeu(UUR) gene commonly associated with the syndrome of mitochondrial encephalopathy, lactic acidosis and strokes (MELAS). Only 6 of the 14 cases (43%) had seizures and recurrent strokes, the core clinical features of the MELAS phenotype. Of the remaining cases, four had an encephalomyopathy with deafness, ataxia and dementia, two had syndromes with progressive external ophthalmoplegia and two had limb weakness alone. Even within the MELAS subgroup, the majority of patients had one or more clinical manifestations considered to be atypical of the MELAS syndrome. They included developmental delay, ophthalmoparesis, pigmentary retinopathy and intestinal pseudo-obstruction. The proportion of mutant mitochondrial DNA (mtDNA) in muscle was generally higher in patients with recurrent strokes than in those without strokes, the highest levels being observed in MELAS cases with early onset disease. Studies of isolated muscle mitochondria identified a range of respiratory chain abnormalities mostly involving Complex I; immunoblots of Complex I in 3 of 10 cases showed selective loss of specific subunits encoded by nuclear genes. In the group as a whole, however, no clear correlations were observed between the severity or extent of the respiratory chain abnormality and clinical phenotype or the proportion of mutant mtDNA in biopsied skeletal muscle. These discrepancies suggest that, in patients harbouring the common MELAS3243 mutation, differences in heteroplasmy and the proportions of mutant mtDNA may not be the sole determinants of disease expression and that additional genetic mechanisms are involved in defining the range of clinical and biochemical phenotypes associated with this aberrant mitochondrial genome.
 ...
PMID:Mitochondrial DNA (mtDNA) diseases: correlation of genotype to phenotype. 759 99

A 16-year-old female presented with clinical, morphologic and molecular features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Her early development was normal. Starting from the age of 14 years, she experienced recurrent episodes of headaches, with vomiting, seizures, transient right hemiparesis and decreased visual acuity. Computed tomographic brain scans revealed calcification in the bilateral basal ganglia. Biopsied specimens from her left biceps brachii and rectus femoris muscles revealed ragged-red fibers and strong succinate dehydrogenase-reactive blood vessels. Electron microscopy revealed paracrystalline inclusions in muscle mitochondria. Analysis of mitochondrial DNA (mtDNA) from blood, hair follicles and muscle specimens showed an A to G point mutation at nucleotide position 3,243 in the transfer RNA(Leu(UUR)). The proportion of mutant mtDNA in the patient's blood was 43%, in hair follicles 62% and in muscle 82%. The patient was followed up for 4 years and had progressive mental deterioration and died of an episode of status epilepticus. This patient and 5 other MELAS patients reported in Taiwan are compared.
 ...
PMID:Heteroplasmic mitochondrial DNA mutation in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. 761 32

The effect of repeated episodes of asphyxia on the fetal cardiovascular system and CNS was examined. The umbilical cord was occluded for 5 min, four times, at 30-min intervals in 11 chronically instrumented fetal sheep (118-126 d). Fetal electrocorticogram (ECoG), cortical impedance, ECG, heart rate, and blood pressure were continuously recorded for 3 d, after which neuronal loss was determined histologically. Each occlusion resulted in fetal hypoxemia and bradycardia accompanied by increased T/QRS ratio. Progressively severe hypotension and lactic acidosis developed during successive occlusions. The ECoG was depressed and cortical impedance increased with each occlusion. During the final occlusion, blood pressure fell to 3.5 +/- 1 kPa and heart rate to 93 +/- 9 bpm, T/QRS ratio increased to 0.44 +/- 0.3, and lactate rose to 7.2 +/- 1.2 mM/L. Three animals died from cardiac fibrillation during recirculation after the third or fourth occlusion. After the asphyxial episodes, blood pressure and heart rate returned to normal, and the T wave was inverted for 310 +/- 155 min. Lactate returned to baseline within 24 h. The ECoG remained depressed for 90 +/- 35 min, and intermittent seizures developed at 3.3 +/- 1.4 h after the last occlusion. Neuronal loss was primarily found in the striatum. The extent of neuronal loss correlated with the degree of hypotension, increase in T/QRS ratio, duration of postasphyxial ECoG depression, and number of seizures. These results indicate that transient asphyxial episodes compromise the ability of the heart to tolerate additional insults and further suggest that neuronal loss is a consequence of cardiovascular compromise secondary to asphyxia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Repeated episodes of umbilical cord occlusion in fetal sheep lead to preferential damage to the striatum and sensitize the heart to further insults. 765 53

A 4-year-old boy presented with developmental delay, aggressive behavior, and incoordination. His EEG showed a diffuse encephalopathy. At age 10 he developed convulsions and severe migraine-like headaches. Muscle wasting, arreflexia, and lactic acidemia following exercise were noted. Electromyography was myopathic and nerve conduction studies revealed a peripheral neuropathy. Muscle biopsy demonstrated variation in fiber size and an excess of lipid droplets. He than had several stroke-like episodes and periods of unconsciousness, associated with severe metabolic acidosis. Muscle cytochrome C oxidase was abnormally low. This boy displayed the classical clinical and biochemical features of MELAS syndrome, namely Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes. Treatment included carnitine, vitamin C, vitamin K, riboflavin, coenzyme Q10, and corticosteroids. He died at the age of 14 years following an episode of seizures, coma, and gastrointestinal hemorrhage. This is the first reported case of MELAS syndrome in Israel.
 ...
PMID:MELAS syndrome: peripheral neuropathy and cytochrome C-oxidase deficiency: a case report and review of the literature. 772 60

Two half-brothers and their mother had symptomatic pyruvate dehydrogenase complex deficiency. The infants had severe congenital lactic acidosis, seizures, and apneic spells and died at the ages 3 and 4 months. The mother was less symptomatic with mental retardation, truncal ataxia, and dysarthria. The residual pyruvate dehydrogenase activities in cultured skin fibroblasts from the 2 infants and their mother were 7, 15, and 10% of control values. Immunoblot analysis showed negligible amounts of E1 alpha and E1 beta subunits of the complex. Northern blot analysis for the E1 alpha subunit showed normal results. In the 2 sons, complementary DNA sequence analysis revealed a cytosine to thymine mutation in exon 4, resulting in a change of arginine 127 to tryptophan in the E1 alpha subunit. Restriction enzyme analysis of the polymerase chain reaction product representing exon 4 of the E1 alpha gene revealed that the mother was a heterozygotes. Complementary DNA restriction analysis and methylation analysis of the X chromosome DXS255 loci revealed skewed activation of the mutant allele, consistent with the deficient pyruvate dehydrogenase activity in the mother's fibroblasts. The milder maternal phenotype is consistent with variable X-inactivation patterns in different organs of female heterozygotes.
 ...
PMID:Pyruvate dehydrogenase deficiency: molecular basis for intrafamilial heterogeneity. 802 67

Two dizygotic twins with myopathy and leukoencephalopathy are described. The female twin had an incomplete form of MELAS syndrome (myopathy, encephalopathy, lactic acidosis, and strokelike episodes) with severe myopathy, epileptic seizures without strokelike episodes. The male twin presented clinical features exclusively of myopathy and subclinical leukoencephalopathy. The MELAS mitochondrial DNA point mutation (MELAS-3243) was found by southern blot and polymerase chain reaction in muscle, skin fibroblasts, and blood of the female twin and was not detected in the skin fibroblasts nor in the blood of the mother, nor in any of the tissues tested in the male twin. The absence of mutation in male twin tissues raises questions about the pathogenetic significance of the mutation in this family.
 ...
PMID:Myo-leukoencephalopathy in twins: study of 3243-myopathy, encephalopathy, lactic acidosis, and strokelike episodes mitochondrial DNA mutation. 812 91

We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese family with confirmed mitochondrial DNA point mutation. Six members of the family including the grandmother, two siblings, and three grandchildren were affected. Among them, action myoclonus was seen in five; short stature, muscle weakness, and mental retardation in four; lactic acidosis, hearing impairment, and ataxia in two; and seizures in one. Muscle biopsy from two affected siblings revealed ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline inclusions. Pedigree analysis suggests a maternal transmission. Analysis of mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide position located in the tRNA(Lys) gene. To our knowledge, this is the first report of MERRF syndrome with such genetic defect from a Chinese family. The present and previous reports support the notion that mitochondrial DNA point mutation at the 8344th nucleotide position is the most common cause of MERRF syndrome.
 ...
PMID:Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese family with mitochondrial DNA point mutation in tRNA(Lys) gene. 793 36

Ethanol intoxication has been widely reported as a cause of lactic acidosis. To determine the frequency and severity of ethanol-induced lactic acidosis, patients who presented to an emergency department with a clinical diagnosis of acute ethanol intoxication and a serum ethanol concentration of at least 100 mg/dL were studied. Arterial blood was sampled for lactate and blood gas determinations. A total of 60 patients (mean age, 41 years) were studied. Twenty-two patients sustained minor trauma. Ethanol concentrations ranged from 100 to 667 mg/dL (mean, 287 mg/dL). Lactate concentrations were abnormal (> 2.4 mmol/L) in seven patients (11.7%). In all cases, blood lactate was less than 5 mmol/L. Of the patients with elevated lactate, other potential causes for lactic acidosis, including hypoxia, seizures, and hypoperfusion, were also present. Only one case with elevated blood lactate concentration had associated acidemia. Significant elevations of blood lactate are uncommon in acute ethanol intoxication. In patients with ethanol intoxication who are found to have lactic acidosis, other etiologies for the elevated lactate level should be considered.
 ...
PMID:Lactic acidosis and acute ethanol intoxication. 828 68

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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>