Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In childhood mitochondrial encephalopathies the common MRI features are bilateral symmetric abnormalities in basal nuclei and brainstem. The presence of diffuse white matter abnormality has been described only in a few cases. Among a series of 110 children with mitochondrial encephalopathies, 8 patients with MR imaging consistent with a leukoencephalopathy were retrospectively evaluated. Diagnosis was based on the recognition of the biochemical defect in muscle homogenate. H-MR spectroscopic imaging was performed in six of them. Biochemical analysis demonstrated a defect of respiratory chain complexes in six patients: complex I in two cases, complex II in two, complex IV in one, multiple complexes defect in one. Pyruvate dehydrogenase deficiency was demonstrated in two patients. MRI showed severe involvement of the brain white matter without significant basal nuclei or brainstem abnormalities. Two patients developed large cystic areas since onset; in two others progressive vacuolisation of affected white matter was seen later in the course of the disease. One patient with pyruvate dehydrogenase deficiency also presented with a diffuse cortical polymicrogyria. H-MR spectroscopic imaging showed a decrease of N-acetylaspartate, choline and creatine with lactate accumulation in five patients, and was normal in one. These findings suggest that mitochondrial disorders should be included in the differential diagnosis of white matter disorders.
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PMID:Cerebral white matter involvement in children with mitochondrial encephalopathies. 1207 88

The effects of normothermia and delayed hypothermia on the levels of N-acetylaspartate (NAA), reduced glutathione (GSH) and the activities of mitochondrial complex I, II-III, IV and citrate synthase were measured in brain homogenates obtained from anaesthetized neonatal pigs following transient in vivo hypoxia-ischaemia. In the normothermic animals there was a significant decrease in complex I activity and in the levels of GSH and NAA when compared to the controls. Delayed hypothermia preserved NAA and GSH at control levels and enhanced the rate of complex II-III activity. There was correlation (R = 0.79) between GSH and NAA levels when data from all three experimental groups were analyzed. Citrate synthase activity was not significantly different in the three groups, indicating maintenance of mitochondrial integrity. These data suggest that delayed hypothermia affords protection of integrated mitochondrial function in the neonatal brain following transient hypoxia-ischaemia.
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PMID:Delayed hypothermia prevents decreases in N-acetylaspartate and reduced glutathione in the cerebral cortex of the neonatal pig following transient hypoxia-ischaemia. 1251 11

Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is the most common childhood mitochondrial encephalopathy, accounting for more than 50% of cases in this age group. Its estimated incidence is 1:40,000 - 1:77,000 liveborn infants a year. LS is a rare progressive multisystem fatal disorder inherited by autosomal recessive, X-linked and maternal transmission. Clinical onset is predominantly in the first two years of life (average: six months); 50% of patients die within a year, even though there are later- and even adult-onset forms with a more protracted evolution. LS is due to a deficit of various respiratory chain and Krebs cycle enzymes resulting in insufficient production of adenosine triphosphate (ATP), in particular cytochrome-c-oxidase (COX), pyruvate carboxylase, pyruvate dehydrogenase complex and complex I of the respiratory chain, which share an autosomal recessive and X-linked mode of transmission. Cases with maternal inheritance (MILS) are due to a mitochondrial DNA (mtDNA) point mutation. LS is clinically heterogeneous in relation to the severity of the metabolic dysfunction and is characterized by muscle involvement and especially CNS disorders, particularly psychomotor retardation, ocular symptoms, hypotonia and pyramidal signs. Death is most commonly due to respiratory failure, status epilepticus and sudden coma. The major neuropathological findings, first described by Leigh in 1951, are symmetrical foci of spongy necrosis associated with vessel proliferation and reactive gliosis in basal nuclei, brainstem and thalamus grey matter. The neuronal metabolic alteration can also affect the white matter, resulting in delayed myelination or hypomyelination. The diagnosis rests on clinical signs, elevated CSF lactate, pyruvate and alanine, and biochemical and neuroradiological data. We describe two patients with LS studied with morphological MR associated with diffusion and spectroscopy techniques to assess the diagnostic potential of standard MR imaging and establish whether the association of functional MR methods can improve its diagnostic accuracy. A case of LS with a post-mortem MR study is also described. Three patients with a diagnosis of LS based on clinical, CSF and laboratory data were studied on a GE SIGNA EXCITE 1.5 T unit using an eight-channel phased-array head coil to acquire standard sequences (SE T1; TSE DP T2; FLAIR) and echo-planar diffusion-weighted sequences (DWI; b= 1000 s/mm2) with calculation of ADC maps. The spectroscopic study used single-voxel (TE/TR ms = 144/1500) and multi-voxel techniques (TE/TR ms = 144/1000) at the level of the basal nuclei. Bilateral and symmetrical involvement of basal nuclei grey matter with T2 hyperintensity was a consistent finding in the morphological MR study. In one patient, associated white matter involvement with T2 hyperintensity in periventricular and retrotrigonal areas reflected delayed myelination or hypomyelination. The deep grey matter changes, sometimes associated with white matter lesions, suggested a diagnosis of subacute necrotizing encephalomyelopathy, in line with the literature. Acute-phase ADC values in affected areas were lower than those of normal grey and white matter and displayed signal hyperintensity on DWI. Reduced ADC values are associated with restricted water diffusivity typical of cytotoxic edema. Spectroscopy showed a high lactate peak, reflecting altered anaerobic glycolysis, and a reduced NAA peak in affected areas, which are however non-specific findings. The most informative study in these patients is standard MR associated with functional techniques, which can confirm the diagnosis obtained with morphological imaging.
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PMID:Leigh Syndrome: an MR Study of Three Cases. 2429 89