title: Thermolabile CPT II variants and low blood ATP levels are closely related to severity of acute encephalopathy in Japanese children.
abstract: Despite the decrease in Reye syndrome after the discontinuation of aspirin, acute encephalopathy (non-Reye syndrome type) has been continually reported in Japan. Recent studies suggested that the thermolabile phenotype of carnitine palmitoyltransferase II (CPT II) variation [F352C] was closely related to the pathomechanism of influenza-associated encephalopathy (IAE) in Japanese, causing mitochondrial ATP utilization failure during periods of high fever, resulting in brain edema. So, we analyzed CPT II polymorphism and peripheral blood ATP levels as a signal of "energy crisis" in 12 and 10 patients with acute encephalopathy, respectively. Out of the 12 patients with acute encephalopathy, six showed thermolabile CPT II variants [F352C], and of these six, two patients died in spite of intensive care. In contrast, the remaining six patients with no thermolabile CPT II variant [F352C] showed a relatively mild clinical course. Blood ATP levels of the 10 patients in the acute phase of encephalopathy were significantly lower than those during the convalescent phase and also those of patients with febrile seizure status. Our data suggest that the thermolabile F352C CPT II variant, found only in Japanese, might be one of the predisposing factors to trigger the pathomechanism of acute encephalopathy in the Japanese population, and that it is causally related to the severity of disease. The decreased blood ATP level seems to reflect systemic mitochondrial dysfunction including the blood brain barrier during the acute phase of encephalopathy.
authors.affiliation: Division of Neurology, National Center for Child Health and Development, 2-10-1 Ohkura, Setagaya-Ku, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kubota
authors.forename: Junji
authors.initials: J
authors.lastname: Chida
authors.forename: Hideki
authors.initials: H
authors.lastname: Hoshino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ozawa
authors.forename: Ayaka
authors.initials: A
authors.lastname: Koide
authors.forename: Hirohumi
authors.initials: H
authors.lastname: Kashii
authors.forename: Akiko
authors.initials: A
authors.lastname: Koyama
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Ai
authors.initials: A
authors.lastname: Hoshino
authors.forename: Miyoko
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Dengbing
authors.initials: D
authors.lastname: Yao
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018792:Encephalitis, Viral / Q000097:blood* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D007564:Japan; D008163:Luminescent Measurements; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D000255:Adenosine Triphosphate; D002334:Carnitine O-Palmitoyltransferase