Takahashi Yutaka, Iida Keiji, Takeno Ryoko, Kitazawa Riko, Kitazawa Sohei, Kitamura Hidetsuna, Fujioka Yoshio, Yamada Hiroyuki, Kanda Fumio, Ohta Shigeo, Nishimaki Kiyomi, Fujimoto Masayo, Kondo Takeshi, Iguchi Genzo, Takahashi Kentaro, Kaji Hidesuke, Okimura Yasuhiko, Chihara Kazuo
Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Endocr J. 2008 Jul;55(3):509-14. doi: 10.1507/endocrj.k07e-091. Epub 2008 Apr 30.
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.
