Analysis of SNPs and enzymatic disorder in the patients of influenza-associated encephalopathy: disorder of fatty acid metabolism in mitochondria induced by high fever
Kido, H.; Yao, D.; Le Trong, Q.; Tsukane, M.; Chida, J.
Nihon Rinsho. Japanese Journal of Clinical Medicine 64(10): 1879-1886
2006
ISSN/ISBN: 0047-1852 PMID: 17037363 Document Number: 604746
To assess the etiology of influenza-associated encephalopathy(IAE), a surveillance effort was conducted during 2000-2005 in Japan. Over half of fatal and handicapped IAE patients exhibited a disorder of mitochondrial beta-oxidation and ATP generation evoked by the thermolabile phenotype of carnitine palmitoyltransferase II variations with transiently elevated serum acylcarnitine during high-grade fever. Model mice having impaired mitochondrial beta-oxidation exhibited significant accumulation of mini-plasmin and up-regulation of trypsin in the cerebral capillaries after infection with influenza A virus, resulting in the destruction of blood-brain barrier and increased brain vascular permeability. Trypsin up-regulation was also evident in the neuronal cells in the hippocampus, suggesting a severe neurologic complication of IAE.