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Query: UMLS:C0751651 (mitochondrial disease)
 1,844 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present ten patients with classical or common migraine of increasing severity accompanied by seizures of multiple patterns and increasing severity leading to episodes of epilepsia partialis continua. Long lasting deficits associated with hypodense lesions on CT and abnormal signals on MRI, then developed. Cortical blindness, cortical deafness and dementia were common. Five of the patients died in 1-10 years. Some of these patients had markers of mitochondrial disease (ragged red fibers and serum lactate elevation) and others with the same clinical picture did not. This group of patients indicates that mitochondrial encephalopathy may exist without evidence of myopathy, that the clinical syndrome is characteristic and that it should suggest the diagnosis even in the absence of muscular abnormalities.
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PMID:Malignant migraine: the syndrome of prolonged classical migraine, epilepsia partialis continua, and repeated strokes; a clinically characteristic disorder probably due to mitochondrial encephalopathy. 311 51

We report the clinical, neuroradiological and biochemical features of a patient with epilepsia partialis continua (EPC). MRI studies disclosed multiple cortico-subcortical areas of abnormal signal intensity. The activity of complex I of the mitochondrial respiratory chain was markedly reduced in skeletal muscle. The biochemical defect was reflected in vivo by a failure of brain and skeletal muscle bioenergetics, as shown by exercise and phosphorus magnetic resonance spectroscopy (31P-MRS) studies. Muscle morphology was repeatedly normal, and molecular genetic analysis of mitochondrial DNA was not informative. On the basis of in vivo and in vitro findings, the observed defect of the mitochondrial respiratory chain was considered the underlying biochemical pathogenesis of the disease. The observation of an oxidative defect in the brain and skeletal muscle of a patient with EPC emphasizes the importance of studying mitochondrial energy metabolism in patients with EPC not associated with primary CNS lesions when clinical and morphological findings suggesting a mitochondrial disorder are lacking. 31P-MRS can be a useful method to uncover deficits of CNS mitochondrial function and provide the indication for further biochemical studies.
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PMID:Epilepsia partialis continua associated with NADH-coenzyme Q reductase deficiency. 760 30

This study was aimed at investigating the value of MRI in the diagnosis of multiple sclerosis. In the Multiple Sclerosis Center of our University, we sorted out of the patients submitted to CSF and MR examinations, only those with clinically unquestionable multiple sclerosis, white matter abnormalities at MRI and normal CSF examination. These 21 patients were submitted to CSF and MRI examinations which were repeated whenever required if image quality was technically suboptimal; a variety of screening tests for different diseases mimicking multiple sclerosis were also performed. In 4 patients with white matter abnormalities at MRI which were considered atypical for multiple sclerosis, at image rereading and after laboratory tests the diagnosis were: coagulopathy, sarcoidosis, vasculitis and CNS lymphoma. In 2 cases with questionable white matter abnormalities at MRI, the final diagnosis were borreliosis and vasculitis. The remaining 15 patients had a diagnosis of multiple sclerosis in all but 3 cases in which subsequent clinical and laboratory examinations demonstrated the presence of vasculitis, embolism from interatrial septal aneurysm and mitochondrial disease. Our study suggests that in the patients with clinical findings of multiple sclerosis and disseminated MR lesions mimicking multiple sclerosis, but no CSF abnormalities, the classical clinical criteria may not be sufficiently specific and other diagnoses must therefore be excluded before making an "unquestionable" diagnosis of multiple sclerosis.
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PMID:[Multiple sclerosis with negative cerebrospinal fluid. Magnetic resonance differential diagnosis]. 787 31

We present a Chinese female infant with an intermittent form of MSUD whose early development was relatively well. A total of three episodes of stupor and metabolic acidosis developed with a concurrent illness after the age of 13 months. The initial analyses of plasma amino acid and urinary organic acid were normal. Initially, an abnormal oral glucose lactate stimulation test and high signal in the bilateral globus pallidus over T2-weighted brain MRI led us to suspect a mitochondrial disorder. The final diagnosis was made after the patient died at 31 months of age.
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PMID:Intermittent form of maple syrup urine disease: report of one case. 947 20

We describe painful subcutaneous lipomatosis in four members of a two-generation family. Lipomas appeared in adulthood, were circumscribed, painful on touch and mainly localized to the trunk and proximal parts of the extremities. The disorder was associated with dysarthria, visual pursuit defect and progressive dystonia. MRI showed bilateral increasing cystic lesions in the basal parts of the putamen. No other abnormalities were detected. The lesions corresponded well with the clinical presentation in the patients. Investigation for mitochondrial disease with muscle biopsy and mitochondrial DNA gave normal results. No consistent biochemical changes were found. The disorder in this family was considered to differ from MERRF with lipomatous lesions and multiple symmetric lipomatosis but compatible with a Dercum disease variant.
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PMID:Dysarthria, progressive parkinsonian features and symmetric necrosis of putamen in a family with painful lipomas (Dercum disease variant). 1207 86

Quantitative MRI and phosphorus magnetic resonance spectroscopy ((31)P-MRS) were used to investigate skeletal muscle metabolism in vivo in patients with dermatomyositis (DM) and polymyositis (PM) in order to evaluate the role of mitochondrial abnormalities in the pathogenesis and clinical expression of these conditions. Nine patients with DM (mean age +/- SD, 57 +/- 14 years) and five with PM (42 +/- 12 years) and with age at disease onset 53 +/- 16 and 38 +/- 12 years, respectively, were included in the study together with 18 age-matched controls. Post-exercise (31)P-MRS indices of muscle oxidative metabolism were all impaired in DM and PM. In both groups of patients, the phosphocreatine and adenosine diphosphate recovery half-times were almost twice as long as in controls (P < 0.05 for each variable) and the maximum rate of mitochondrial ATP production was half that found in normal subjects (P < 0.001). The rate of proton efflux from muscle fibres was significantly reduced in DM (P < 0.001) and PM (P = 0.02). The impairment of (31)P-MRS recovery indices in DM and PM patients was similar to that found in a group of 10 patients with a primary mitochondrial disorder that showed a normal proton efflux rate. There was no correlation between the MRS-detectable abnormalities and the degree of inflammation or fatty infiltration of the muscle, as measured by MRI. The in vivo findings in DM and PM patients indicate impaired muscle aerobic function, which, considering the reduced proton efflux, is likely to be secondary to an impaired blood supply. Our results suggest that the abnormal mitochondria seen in some muscle biopsies are unlikely to be the primary cause of the oxidative insufficiency in these patients.
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PMID:Reduced oxidative phosphorylation and proton efflux suggest reduced capillary blood supply in skeletal muscle of patients with dermatomyositis and polymyositis: a quantitative 31P-magnetic resonance spectroscopy and MRI study. 1207 12

Alpers-Huttenlocher syndrome (AHS) is a rare mitochondrial disorder of childhood onset that is characterized by progressive encephalopathy and hepatopathy. MRI studies are rare and have not added substantial information to the pathogenesis of the encephalopathy. Diffusion-weighted MRI (DWI) and MR spectroscopy (MRS) were used in a patient with AHS during acute clinical deterioration and after improvement. DWI detected signal hyperintensity in several brain areas not restricted to any vascular territory. MRS revealed an unequivocal lactate peak and a reduced N-acetyl-aspartate-creatinine (NAA/Crea) ratio. DWI signal hyperintensity was correlated with neurologic symptoms and decreased after clinical improvement. Potentially reversible neuronal cytotoxic edema resulting from acute impairment of mitochondrial function is strongly suggested to be an important pathogenetic mechanism in AHS encephalopathy.
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PMID:Detection of acute cytotoxic changes in progressive neuronal degeneration of childhood with liver disease (Alpers-Huttenlocher syndrome) using diffusion-weighted MRI and MR spectroscopy. 1221 35

The Mohr-Tranebjaerg syndrome (MTS) is a rare neurodegenerative disorder characterized by early-onset deafness, dystonia and further neurological abnormalities such as cortical blindness, spasticity, dementia and mental retardation. Causative mutations were identified within the deafness-dystonia peptide (DDP1/TIMM8a) gene on the X-chromosome. The DDP1 protein is located in the intermembrane space of human mitochondria. Here, it acts in a complex together with its partner protein Tim13 in a chaperone-like manner to facilitate the import of nuclear-encoded precursor proteins into the mitochondrial inner membrane. Thus, MTS is a novel type of mitochondrial disorder. To obtain more insight into the pathophysiology of this neurodegenerative disorder, we performed for the first time a comprehensive clinical and functional characterization of a patient suffering from MTS. This patient exhibited a typical combination of deafness, dystonia and visual loss. Sequence analysis of the patient's DDP1 gene revealed a G to C transversion at nucleotide position 38 of the first exon. The mutation affects the ATG start codon, thereby changing methionine to isoleucine (M1I), and leads to a complete absence of the DDP1 protein. In addition, the partner protein Tim13 was found to be significantly reduced, suggesting that Tim13 requires the presence of DDP1 for its stabilization. The assessment of mitochondrial functions showed the enzyme activities of the mitochondrial energy-generating systems to be normal in the muscle biopsy. Structural abnormalities or aggregations of mitochondria were absent. Electron microscopy revealed only a mild neurogenic atrophy. Neurophysiological investigations showed cochlear dysfunction and disturbance of visual pathways. PET and MRI studies revealed a multifocal pattern of neurodegeneration with hypometabolic areas predominantly located over the right striatum and parietal cortex and marked atrophy of the occipital lobes. Although the visual loss is caused predominantly by neurodegeneration of the visual cortex, degeneration of the retina and the optic nerve contributes to the visual impairment. The pathological changes in basal ganglia and sensory cortex demonstrate the disintegration of subcortico-cortical circuits and correlate well with the clinical presentation of multifocal dystonia. The data presented here showed that, in contrast to most of the known mitochondrial disorders, MTS appears not to be associated with a functional defect of the energy generation system of the mitochondria. Whereas the specific mitochondrial dysfunction leading to neuronal loss in MTS remains to be clarified, the electrophysiological and neuroimaging findings allowed the multifocal manifestation of neurodegenerative lesions in MTS to be characterized specifically.
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PMID:Clinical and molecular findings in a patient with a novel mutation in the deafness-dystonia peptide (DDP1) gene. 1280 99

It is well known that morphological changes at the cellular level occur in muscle of patients with mitochondrial myopathy (MM), but changes in muscle structure with fat infiltration and gross variation of muscle fiber size with giant fibers, normally encountered in the muscular dystrophies, have typically not been associated with mitochondrial disease. We investigated gross and microscopic muscle morphology in thigh muscles by muscle biopsy and MRI in 16 patients with MM, and compared findings with those obtained in muscular dystrophy patients and healthy subjects. Changes of muscle architecture, similar to those found in the group of muscular dystrophy patients occurred consistently in patients with a high mutation load for single, largescale deletions of mtDNA, but were absent in all patients with the 3243A-->G mtDNA point mutation. Dystrophic changes of muscle architecture were also present in one MM patient with a unique, sporadic mutation in the mtDNA tRNA(Met) gene. These findings provide evidence that morphological changes in muscle of MM patients are common and may resemble those of muscular dystrophies, but that development of dystrophic-like changes in muscle relate to genotype.
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PMID:Muscle structural changes in mitochondrial myopathy relate to genotype. 1464 49

Leber hereditary optic neuropathy (LHON)/pediatric onset dystonia is associated with a G to A transition at nucleotide position (np) 14459, within the mitochondrial DNA (mtDNA)-encoded ND6 gene. This mutation has been reported in families presenting with LHON alone, LHON plus dystonia, or pediatric dystonia with typical age of onset less than 5 years. The mutation changes a moderately conserved alanine to a valine at amino acid residue 72, which is within the most evolutionarily conserved region of the ND6 protein. Pediatric onset disease is associated with basal ganglia dysfunction, spasticity, and encephalopathy. We report a family with G14459A mtDNA mutation and a broad spectrum of clinical manifestation. The proband was a 3-year-old girl with anarthria, dystonia, spasticity, and mild encephalopathy. MRI of the brain demonstrated bilateral, symmetric basal ganglia lucencies associated with cerebral and systemic lactic acidosis. Her maternal first cousin presented with a new onset limp and mild hemiparesis along with similar MRI findings with a much milder phenotype. Additional investigation of the family members with the mutation has revealed both asymptomatic and symptomatic individuals with variable clinical and laboratory features of mitochondrial disease. This study re-emphasizes the heterogeneous clinical manifestation of homoplasmic G14459A mtDNA mutation even within the same family, and supports the hypothesis that nuclear genes may play a role in modifying the clinical expression of mitochondrial disease. Published 2003 Wiley-Liss, Inc.
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PMID:Variable clinical manifestation of homoplasmic G14459A mitochondrial DNA mutation. 1473 85


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