Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a pair of brothers who have leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia. Both presented initially with seizures in the early postnatal period. They have significant developmental delay, and brain MRIs demonstrate leukoencephalopathy, characterized by profound hypomyelination. They have developed arthritis, which in one brother has required chronic treatment; and persistent intermittent diarrhea, necessitating treatment for inflammatory bowel disease. Finally, they have had multiple hospitalizations, including several for sepsis; an immunological analysis revealed that they have IgG1-subclass hypogammaglobulinemia and low B cell levels. There is no family history of similar problems, and these brothers have an unaffected brother. We believe this constellation of symptoms represents a novel syndrome: LACH syndrome (leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia). The etiology of this syndrome remains unknown despite extensive investigations.
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PMID:Leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia (LACH) in two brothers: a novel syndrome? 1521 57

Neurons uniquely antagonize fatty acid utilization by hydrolyzing the activated form of fatty acids, long chain acyl-CoAs, via the enzyme acyl-CoA thioesterase 7, Acot7. The loss of Acot7 results in increased fatty acid utilization in neurons and exaggerated stimulus-evoked behavior such as an increased startle response. To understand the contribution of Acot7 to seizure susceptibility, we generated Acot7 knockout (KO) mice and assayed their response to kainate-induced seizures. Acot7 KO mice exhibited potentiated behavioral and molecular indices of seizure severity following kainic acid administration, suggesting that fatty acid metabolism in neurons can be a critical regulator of neuronal activity. These data are consistent with the presentation of seizures in a human with genomic deletion of ACOT7 demonstrating the conservation of function across species. To further understand the metabolic complications arising from a deletion in Acot7, we subjected Acot7 KO mice to a high-fat diet. While the loss of Acot7 did not result in metabolic complications following a normal chow diet, a high-fat diet induced greater body weight gain, adiposity, and glucose intolerance in Acot7 KO mice. These data demonstrate that Acot7, a fatty acid metabolic enzyme highly enriched in neurons, regulates both brain-specific metabolic processes related to seizure susceptibility and the whole body response to dietary lipid.
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PMID:Loss of ACOT7 potentiates seizures and metabolic dysfunction. 3103 8