title: Hepatic failure and enhanced oxidative stress in mitochondrial diabetes.
abstract: Mitochondrial diabetes is characterized by diabetes and hearing loss in maternal transmission with a heteroplasmic A3243G mutation in the mitochondrial gene. In patients with the mutation, it has been reported that hepatic involvement is rarely observed. We demonstrated a case of hypertrophic cardiomyopathy and hepatic failure with mitochondrial diabetes. To clarify the pathogenesis we analyzed the mitochondrial ultrastructure in the myocytes, the reactive oxygen species (ROS) production in the liver and the status of heteroplasmy of the mitochondrial A3243G mutation in the organs involved. In cardiomyocytes and skeletal muscle, electron microscopic analysis demonstrated typical morphological mitochondrial abnormalities. Immunohistochemical analysis demonstrated enhanced ROS production associated with marked steatosis in the liver, which is often associated with mitochondrial dysfunction. Analysis of the A3243G mutation revealed a substantial ratio of heteroplasmy in these organs including the liver. The presence of steatosis and enhanced oxidative stress in the liver suggested that hepatic failure was associated with mitochondrial dysfunction.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Keiji
authors.initials: K
authors.lastname: Iida
authors.forename: Ryoko
authors.initials: R
authors.lastname: Takeno
authors.forename: Riko
authors.initials: R
authors.lastname: Kitazawa
authors.forename: Sohei
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Hidetsuna
authors.initials: H
authors.lastname: Kitamura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Fumio
authors.initials: F
authors.lastname: Kanda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishimaki
authors.forename: Masayo
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondo
authors.forename: Genzo
authors.initials: G
authors.lastname: Iguchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hidesuke
authors.initials: H
authors.lastname: Kaji
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Okimura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chihara
mesh_terms: D001344:Autopsy; D048909:Diabetes Complications / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics*; D017809:Fatal Outcome; D050259:Genes, Mitochondrial / Q000502:physiology; D006801:Humans; D017093:Liver Failure / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D012356:RNA, Transfer, Leu / Q000235:genetics
chemical_list: D012356:RNA, Transfer, Leu