1/51. lipomatosis, proximal myopathy, and the mitochondrial 8344 mutation. A lipid storage myopathy?Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial dna, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We report on two families harboring the 8344 mutation. The patients presented with MSL and myopathy, expressed as limb girdle weakness in index cases and as exercise intolerance in the others. All muscle biopsies performed showed lipid storage apart from RRF and respiratory chain complexes deficiency. A possible explanation for both adipose proliferation and lipid storage myopathy in these cases is a disturbance in intermediary lipid metabolism secondary to mitochondrial respiratory chain deficiency that could be related via carnitine deficiency.- - - - - - - - - - ranking = 1keywords = myoclonic epilepsy, myoclonic, epilepsy (Clic here for more details about this article) |
2/51. Evidence that Alpers-Huttenlocher syndrome could be a mitochondrial disease.We report an 11-year-old boy with a slight developmental delay and epilepsy. After he was placed on valproate, he developed hepatic failure and increasing neurologic symptoms, including epilepsia partialis continua, and died. autopsy findings in liver and cerebrum were consistent with progressive neuronal degeneration of childhood with liver disease, also called Alpers-Huttenlocher syndrome. Ragged red fibers and cytochrome c oxidase negative fibers were present in muscle. These results suggest that Alpers-Huttenlocher syndrome, at least in some patients, is a mitochondrial disease.- - - - - - - - - - ranking = 0.0075700292708214keywords = epilepsy (Clic here for more details about this article) |
3/51. Thalamic activation in photic myoclonus.Regional cerebral blood flow (rCBF) during photic myoclonus was studied by means of positron emission tomography in a 51-year-old male patient suffering from MERRF (myoclonic epilepsy with ragged-red fibres). Frequencies of 3 Hz and 5 Hz flash stimulation were used. Both frequencies elicited paroxysmal EEG-abnormalities but only the higher frequency induced generalized myoclonic jerks. We found a left dominated significant increase of rCBF in the thalamus during myoclonus. The thalamic asymmetry was significant when tested with an ROI approach. The myoclonic activity was accompanied by significantly increased activity in the supplementary motor cortex (SMA). Decreases in rCBF were seen in the limbic, temporal and occipital areas during photic stimulation at both flash frequencies, more expressed during myoclonus. The findings observed in this patient indicate a thalamic focus for photic myoclonus in MERRF. We suggest that photic stimulation induced an abnormal discharge in the thalamus, which was fed forwards via thalamo-cortical connections to the precentral motor cortex, to produce the muscle jerks.- - - - - - - - - - ranking = 1.1627046551208keywords = myoclonic epilepsy, myoclonic, epilepsy (Clic here for more details about this article) |
4/51. G8363A mutation in the mitochondrial dna transfer ribonucleic acidLys gene: another cause of Leigh syndrome.We identified a G-->A transition at nt-8363 in the mitochondrial dna transfer ribonucleic acidLys gene in blood and muscle from a 13-month-old girl who had clinical and neuroradiologic evidence of Leigh syndrome and died at age 27 months. The mutation was less abundant in the same tissues from the patient's mother, who developed myoclonus epilepsy with ragged red fibers (MERRF) in her late 20s. In both mother and daughter, muscle histochemistry showed ragged red and cytochrome c oxidase-negative fibers and biochemical analysis showed partial defects of multiple respiratory-chain enzymes. A maternal half-sister of the proband had died at 2.5 years of age from neuropathologically proven Leigh syndrome. The G8363A mutation, which previously had been associated with cardiomyopathy and hearing loss, MERRF, and multiple lipomas, also should be included in the differential diagnosis of maternally inherited Leigh syndrome.- - - - - - - - - - ranking = 0.0075700292708214keywords = epilepsy (Clic here for more details about this article) |
5/51. A case of MERRF associated with chronic pancreatitis.We report the first case to our knowledge of chronic pancreatitis associated with mitochondrial encephalopathy with the A8344G mitochondrial dna (mtDNA) mutation. This 10-year-old-girl had suffered from recurrent abdominal pain with elevated serum amylase and lipase since the age of 6, and easy fatigability, tremor and astatic seizures since the age of 8. A biopsy of quadriceps muscle revealed ragged-red-fibers and cytochrome c oxidase deficiency. Analysis of mtDNA in peripheral blood identified an A8344G mutation in the mitochondrial tRNA(Lys) gene. Taken together with physical signs of myoclonic seizures and cerebellar dysfunction, we diagnosed her as myoclonic epilepsy with ragged-red fibers associated with chronic pancreatitis. Although no association between mitochondrial disease and pancreatitis has yet been established, this case suggests it is necessary to consider the participation of mitochondrial abnormality in the pathogenesis of recurrent pancreatitis.- - - - - - - - - - ranking = 1.0813523275604keywords = myoclonic epilepsy, myoclonic, epilepsy (Clic here for more details about this article) |
6/51. Audiological findings in patients with myoclonic epilepsy associated with ragged-red fibres.Sensorineural hearing loss is a common symptom in patients with myoclonic epilepsy associated with ragged-red fibres (MERRF), one of the mitochondrial encephalomyopathies, although the lesion causing hearing loss in such cases remains unknown. Here we describe the audiological features in three MERRF patients, all of whom exhibited a point mutation in their mitochondrial dna at nucleotide 8344. Pure-tone threshold audiometry revealed bilateral, sloping-type, sensorineural hearing loss in all three patients. Distortion product otoacoustic emissions, electrocochleography, and auditory brainstem responses were variable, even differing between the right and left ears of the same patient. Taken together, our findings suggest that the primary lesion underlying hearing loss in MERRF patients is in the cochlea, although a retrocochlear lesion may be involved in some patients.- - - - - - - - - - ranking = 5keywords = myoclonic epilepsy, myoclonic, epilepsy (Clic here for more details about this article) |
7/51. seizures in myoclonic epilepsy with ragged-red fibers detected by dna analysis: a case report.A 19-year-old Thai woman presented with progressive ataxia and generalized tonic-clonic seizures. Later on, she developed status epilepticus. blood was tested by molecular dna analysis which showed A8344G mitochondrial dna mutation associated with myoclonic epilepsy with ragged-red fibers (MERRF). We confirmed this finding in other members of this family. This is an interesting case report in thailand of MERRF identified to have A-->G transition mutation at nucleotide 8344 of mitochondrial tRNA(lys) gene without ragged-red fibers from histopathologic studies of muscle. Molecular genetic analysis in suspicious cases of mitochondrial disorders is necessary for proper management and genetic counseling.- - - - - - - - - - ranking = 5keywords = myoclonic epilepsy, myoclonic, epilepsy (Clic here for more details about this article) |
8/51. The A8344G mutation in mitochondrial dna associated with stroke-like episodes and gastrointestinal dysfunction.We report an unusual case of encephalo-entero-myopathy associated with the A8344G mutation in the tRNA(Lys) gene of mitochondrial dna (mtDNA). This patient had mitochondrial myopathy, multiple lipomatosis, mild hearing loss, stroke-like episodes, and paralytic ileus, but she lacked the canonical clinical features of MERRF, myoclonus, epilepsy, or ataxia. We conducted genetic, biochemical, histochemical, and immunohistochemical studies in skeletal muscle, brain, intestine, and lipoma tissue. The mutation was abundant in all tissues, and cytochrome c oxidase (COX) activity was selectively decreased in brain and small intestine. COX deficiency was also documented histochemically and immunohistochemically in the small intestine, suggesting that mitochondrial dysfunction played a role in the pathogenesis of paralytic ileus. This case illustrates an unusual and dramatic clinical phenotype of the A8344G mutation, characterized by stroke-like episodes and acute ileus.- - - - - - - - - - ranking = 0.0075700292708214keywords = epilepsy (Clic here for more details about this article) |
9/51. A novel mitochondrial tRNA(Leu(UUR)) mutation in a patient with features of MERRF and kearns-sayre syndrome.In a patient with clinical features of both myoclonus epilepsy ragged-red fibers (MERRF) and kearns-sayre syndrome (KSS), we identified a novel guanine-to-adenine mitochondrial dna (mtDNA) mutation at nucleotide 3255 (G3255A) of the tRNA(Leu(UUR)) gene. Approximately 5% of the skeletal muscle fibers had excessive mitochondria by succinate dehydrogenase histochemistry while a smaller proportion showed cytochrome c oxidase (COX) deficiency. In skeletal muscle, activities of mitochondrial respiratory chain complexes I, I III, II III, and IV were reduced. The G3255A transition was heteroplasmic in all tissues tested: muscle (53%), urine sediment (67%), peripheral leukocytes (22%), and cultured skin fibroblasts (< 2%). The mutation was absent in 50 control dna samples. Single-fiber analysis revealed a higher proportion of mutation in COX-deficient RRF (94% /- 5, n = 25) compared to COX-positive non-RRF (18% /- 9, n = 21). The identification of yet another tRNA(Leu(UUR)) mutation reinforces the concept that this gene is a hot-spot for pathogenic mtDNA mutations.- - - - - - - - - - ranking = 0.0075700292708214keywords = epilepsy (Clic here for more details about this article) |
10/51. Use of single strand conformation polymorphism analysis to detect point mutations in human mitochondrial dna.myoclonus epilepsy with ragged-red fibers (MERRF) has been shown to be associated with a specific point mutation at the nucleotide 8344 in the tRNA(Lys) gene of mitochondrial dna (mtDNA). We screened 6 patients with clinically diagnosed MERRF and 1 patient with ocular myopathy for point mutations in the tRNA(Lys) gene, using single strand conformation polymorphism (SSCP) analysis, which can detect even a 1-basepair difference between 2 dna sequences. Using SSCP and consequent dna sequencing, we identified the known MERRF mutation in 4 out of 6 MERRF patients, as well as in 1 patient with a new clinical phenotype associated with this mutation: progressive external ophthalmoplegia, muscle weakness and a lipoma, but no myoclonus or epilepsy. Two of the patients with clinical MERRF had neither the MERRF-mutation nor any other mutations in the tRNA(Lys) gene. Using SSCP analysis, we also detected a new polymorphism in 1 patient. Thus, SSCP analysis can be applied to search effectively and rapidly for point mutations or polymorphisms in mitochondrial dna.- - - - - - - - - - ranking = 0.015140058541643keywords = epilepsy (Clic here for more details about this article) |
| | Next -> |