1/29. Mitochondrial disease and stroke.BACKGROUND AND PURPOSE: It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. methods: patients aged stroke Unit from January 1999 to May 2000 with a diagnosis of ischemic stroke of unknown origin, were included in the study. All of them had full biochemical and hematologic tests, neuroimaging studies, transesophageal echocardiography, and extracranial and transcranial Doppler sonography. Patent foramen ovale was ruled out. lactic acid concentrations were measured after anaerobic exercise of the forearm, and a morphological, biochemical, and molecular study after biceps muscle biopsy was performed. RESULTS: Of the 18 patients so far included, 3 (17%) presented lactic acid hyperproduction after physical exercise, and 6 (33%) showed deficit of the mitochondrial respiratory chain complexes. The molecular analyses have confirmed mitochondrial mutations at base pairs 3243 (characteristic of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes [MELAS]), 4216, and 15 928. CONCLUSIONS: These results suggest that ischemic stroke may be the only manifestation or the initial manifestation of a mitochondrial disorder.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
2/29. Parkinson's disease associated with impaired oxidative phosphorylation.Parkinson's disease may be due to primary or secondary oxidative phosphorylation (OXPHOS) defects. In a 76-year-old man with Parkinson's disease since 1992, slightly but recurrently elevated creatine phosphokinase, recurrently elevated blood glucose, thickening of the left ventricular myocardium, bifascicular block and hypacusis were found. Cerebral MRI showed atrophy, periventricular demyelination, multiple, disseminated, supra- and infratentorial lacunas, and haemosiderin deposits in both posterior horns. Muscle biopsy showed typical features of an OXPHOS defect. Whether the association of Parkinson's disease and impaired OXPHOS was causative or coincidental remains unknown. Possibly, the mitochondrial defect acted as an additional risk factor for Parkinson's disease or the OXPHOS defect worsened the preexisting neurological impairments by a cumulative or synergistic mechanism. In conclusion, this case shows that Parkinson's disease may be associated with a mitochondrially or nuclearly encoded OXPHOS defect, manifesting as hypacusis, myopathy, axonal polyneuropathy, cardiomyopathy and recurrent subclinical ischaemic strokes and haemorrhages.- - - - - - - - - - ranking = 2keywords = myopathy (Clic here for more details about this article) |
3/29. External ophthalmoplegia with severe progressive multiorgan involvement associated with the mtDNA A3243G mutation.BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) may be related to primary nuclear dna or mitochondrial (mt)dna mutations. The A3243G mtDNA point mutation most frequently causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, but also has been associated with other phenotypes including CPEO, migraine, seizure, diabetes, and sensorineural hearing loss. CASE DESCRIPTION: We report a 38-year-old white man with seizures and progressive difficulties of infantile origin including CPEO, sensorineural hearing loss, cataracts, migraines, multiple endocrinopathy, myopathy, and cardiomyopathy. Moderate hearing loss in association with CPEO, diabetes mellitus, or migraines were noted in the proband's maternal grandmother, great aunt, mother, and three sisters, suggesting either an autosomal dominant or maternal inheritance. Detailed histological and biochemical analysis of the proband's biopsied muscle specimen revealed severe abnormalities compatible with a mitochondrial disease. MtDNA analysis excluded large-scale deletions, but revealed a heteroplasmic A to G transition at nt3243 in 56.4% and 27.4% of molecules in muscle and white blood cells, respectively. CONCLUSION: We discuss possible causes of this intrafamilial heterogeneity of phenotypes associated with the A3243G mtDNA mutation.- - - - - - - - - - ranking = 32.87582768481keywords = ophthalmoplegia, myopathy (Clic here for more details about this article) |
4/29. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride.The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-coa dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders.- - - - - - - - - - ranking = 6keywords = myopathy (Clic here for more details about this article) |
5/29. Familial childhood onset neuropathy and cirrhosis with the 4977bp mitochondrial dna deletion.The common 4977 base pair mitochondrial deletion has been identified in association with a number of distinct clinical phenotypes. These include the kearns-sayre syndrome, the Pearson marrow-pancreas syndrome, and chronic progressive external ophthalmoplegia. We report the clinical and pathological findings in two siblings in whom the 4977 base pair mitochondrial dna deletion was identified in muscle-derived mitochondrial dna. One sibling manifested early onset liver and renal failure, and both developed prominent peripheral sensorimotor neuropathy. These clinical findings have not been previously described in association with the 4977bp mtDNA deletion and thus represent a further expansion of the spectrum of mitochondrial disease.- - - - - - - - - - ranking = 44.645515107183keywords = chronic progressive, ophthalmoplegia (Clic here for more details about this article) |
6/29. Mitochondrial disease mimicking polymyositis: a case report.The authors report on a 34-year-old woman who had developed severe weakness and reduction in grip strength in both upper and lower limbs. Laboratory blood tests revealed increased levels of muscle enzyme. The presence of progressive bilateral ptosis and external ophthalmoplegia raised the suspicion of a mitochondrial disease, subsequently confirmed by deltoid biopsy and genetic analysis of mitochondrial dna that showed a deletion indicative of kearns-sayre syndrome. In this report we emphasise the need for a differential diagnosis between myositis and other myopathies, particularly the mitochondrial ones.- - - - - - - - - - ranking = 6.175165536962keywords = ophthalmoplegia (Clic here for more details about this article) |
7/29. The length of cytochrome c oxidase-negative segments in muscle fibres in patients with mtDNA myopathy.Heteroplasmic mitochondrial dna mutations often cause a skeletal myopathy associated with a mosaic distribution of cytochrome c oxidase-deficient muscle fibres. The function of an individual muscle fibre is dependent upon the metabolic activity throughout its length, but little is known about the length of cytochrome c oxidase-deficient segments in human skeletal muscle in patients with mitochondrial disease. We studied cytochrome c oxidase activity by serial section analysis of quadriceps muscle from two patients. We observed a striking variation in the length of the cytochrome c oxidase-negative segments. The shortest segments were 10 microm long, and the longest segment was the entire length of the larger biopsy (> or =1.2 mm). The lengths of the cytochrome c oxidase-negative segments were generally shorter in the less severely affected biopsy, and we frequently observed non-contiguous segments of cytochrome c oxidase deficiency within the same muscle fibre. The findings have important implications for our understanding of the pathogenesis and progression of mitochondrial dna myopathy.- - - - - - - - - - ranking = 6keywords = myopathy (Clic here for more details about this article) |
8/29. Mitochondrial fatty acid oxidation disorders in Thai infants: a report of 3 cases.Three infants with documented mitochondrial fatty acid oxidation disorders are described in this report. Case 1. Carnitine/acylcarnitine translocase deficiency. (CACT) (OMIM 212138) A two-day-old male developed sudden cardiac arrest 48 hours postpartum, with a previous history of early death (day 2) in siblings with a history of parental consanguinity; somnolence, inactivity, refusal to suck within 24 h, hepatomegaly, persistent hypoglycemia, hypocalcemia, hyperkalemia and severe metabolic acidosis prior to cardiac arrest. Dried blood spots by tandem mass spectrometry demonstrated 10 x elevation of palmitoylcarnitine, moderate elevation of oleylcarnitine, steroylcarnitine and myristoylcarnitine. Case 2. Medium chain acyl CoA dehydrogenase (MCAD) deficiency. (OMIM 212139) A six-week-old male infant, developed sudden cardiac arrest after contacting a viral illness, resuscitated successfully in the first episode, only to succumb during the second episode, 2 weeks apart. plasma acylcarnitine via tandem mass spectrometry was reported normal; however, urine organic acids via gas liquid chromatography and mass spectrometry demonstrated characteristic metabolites consistent with MCADD. Case 3. Carnitine deficiency, systemic primary. (CDSP) (OMIM 212140) A one-year-old girl with progressive dyspnea since birth and a history of parental consanguinity. Severe dilated cardiomyopathy with episodes of cardiac decompensations, hepatomegaly, anemia, generalized hypotonia, but no hypoglycemia were demonstrated prior to cardiac arrest. Extremely low carnitine level noted in dried blood spots via tandem mass spectrometry.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
9/29. Clinical features and neuroradiological findings of mitochondrial pathology in six neonates.OBJECTS: We hoped to itemize the clinical and neuroradiological features of six neonates with mitochondrial disorders. methods: We examined a case series of six neonates. The diagnosis of mitochondrial cytopathy was made on the basis of spectrophotometric measurements of respiratory chain enzyme activities in skeletal muscle biopsy specimens. Magnetic resonance (MR) imaging was performed in all cases. CONCLUSIONS: The antenatal onset in five cases and the lack of any symptom-free interval are suggestive of fetal expression of the disease. No specific symptoms were found: arthrogryposis congenita multiplex in one, progressive hepatocellular dysfunction in three, encephalomyelopathy and cardiomyopathy in four. Complex I deficiency was found in three patients, while one patients had a defect of complex IV and the last a combined defect of complexes I and IV. Neuroradiological findings were either cerebral atrophy or white matter abnormalities of the brain stem in all cases but one and gave additional information, because clinical symptoms are not quite specific. The combination of clinical and MRI findings in neonatal cases can rule out hypoxic ischemic encephalopathy, which suggests an additional screening method to look for mitochondrial disorder.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
10/29. Muscle glycogenosis and mitochondrial hepatopathy in an infant with mutations in both the myophosphorylase and deoxyguanosine kinase genes.OBJECTIVES: To document 2 apparently incongruous clinical disorders occurring in the same infant: congenital myopathy with myophosphorylase deficiency (McArdle disease) and mitochondrial hepatopathy with liver failure and mitochondrial dna depletion. methods: An infant girl born to consanguineous Moroccan parents had severe congenital hypotonia and hepatomegaly, developed liver failure, and died at 5 months of age. We studied muscle and liver biopsy specimens histochemically and biochemically, and we sequenced the whole coding regions of the deoxyguanosine kinase (dGK) and myophosphorylase (PYGM) genes. RESULTS: Muscle biopsy specimens showed subsarcolemmal glycogen accumulation and negative histochemical reaction for phosphorylase. Liver biopsy specimens showed micronodular cirrhosis and massive mitochondrial proliferation. Biochemical analysis showed phosphorylase deficiency in muscle and cytochrome c oxidase deficiency in liver. We identified a novel homozygous missense G-to-A mutation at codon 456 in exon 11 of PYGM, as well as a homozygous 4-base pair GATT duplication (nucleotides 763-766) in exon 6 of dGK, which produces a frame shift and a premature TGA stop codon at nucleotides 766 to 768, resulting in a truncated 255-amino acid protein. Both mutations were absent in 100 healthy individuals. CONCLUSIONS: Our data further expand the genetic heterogeneity in patients with McArdle disease; confirm the strong relationship between mitochondrial dna depletion syndrome, liver involvement, and dGK mutations; and suggest that genetic "double trouble" should be considered in patients with unusual severe phenotypes.- - - - - - - - - - ranking = 1keywords = myopathy (Clic here for more details about this article) |
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