Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of congenital lactic acidosis associated with pyruvate carboxylase deficiency are described. One 2-mo-old infant had a fulminant clinical course with extremely severe intractable acidosis and died after 48 h in hospital. The second infant, aged 2 1/2 mo, had a milder clinical course, characterized by moderate acidosis and frequent convulsive episodes. He died at the age of 3 mo due to respiratory arrest following prolonged status epilepticus. Pyruvate carboxylase activity in liver biopsy specimens obtained from the two patients was 1 and 50% of normal, respectively. Both patients failed to respond to treatment, including massive doses of thiamine and high serum levels of lactate and pyruvate were found throughout their illnesses. Cerebral autopsy performed in both cases was unremarkable. Absence of neuropathological findings ruled out the possibility of Leigh's disease.
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PMID:Congenital lactic acidosis associated with pyruvate carboxylase deficiency. 679 24

Triheptanoin, the triglyceride of heptanoate, is anticonvulsant in various epilepsy models. It is thought to improve energy metabolism in the epileptic brain by re-filling the tricarboxylic acid (TCA) cycle with C4-intermediates (anaplerosis). Here, we injected mice with [1,2-(13) C]glucose 3.5-4 weeks after pilocarpine-induced status epilepticus (SE) fed either a control or triheptanoin diet. Amounts of metabolites and incorporations of (13) C were determined in extracts of cerebral cortices and hippocampal formation and enzyme activity and mRNA expression were quantified. The percentage enrichment with two (13) C atoms in malate, citrate, succinate, and GABA was reduced in hippocampal formation of control-fed SE compared with control mice. Except for succinate, these reductions were not found in triheptanoin-fed SE mice, indicating that triheptanoin prevented a decrease of TCA cycle capacity. Compared to those on control diet, triheptanoin-fed SE mice showed few changes in most other metabolite levels and their (13) C labeling. Reduced pyruvate carboxylase mRNA and enzyme activity in forebrains and decreased [2,3-(13) C]aspartate amounts in cortex suggest a pyruvate carboxylation independent source of C-4 TCA cycle intermediates. Most likely anaplerosis was kept unchanged by carboxylation of propionyl-CoA derived from heptanoate. Further studies are proposed to fully understand triheptanoin's effects on neuroglial metabolism and interaction.
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PMID:Triheptanoin partially restores levels of tricarboxylic acid cycle intermediates in the mouse pilocarpine model of epilepsy. 2423 46

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