Hayashi Hisao, Hattori Ai, Tatsumi Yasuaki, Hayashi Kazuhiko, Katano Yoshiaki, Ueyama Jun, Wakusawa Shinya, Yano Motoyoshi, Goto Hidemi
Department of Medicine, Aichi Gakuin University School of Pharmacy, Kusumoto-cho, Chikusa-ku, Nagoya, 464-8650, Japan,
Med Mol Morphol. 2013 Sep;46(3):133-40. doi: 10.1007/s00795-013-0015-2. Epub 2013 Jan 22.
Wilson disease (WD) is a major type of primary copper toxicosis associated with hypoceruloplasminemia, while idiopathic copper toxicosis (ICT) is a minor type characterized by normoceruloplasminemia. Because ceruloplasmin is the major circulating ferroxidase, iron metabolism may be affected in patients with WD. Biopsied liver specimens obtained from patients with primary copper toxicosis were fixed with glutaraldehyde solution and embedded in epoxy resin. Ultrathin sections that had or had not been stained with uranyl acetate solution were examined under an electron microscope equipped with an energy dispersive X-ray analyzer. A 7-year-old boy with WD was free from any metal overloading at the pre-treatment stage. Pre-treatment liver specimens of another 16 patients showed a variety of copper and iron overload patterns, from isolated copper to evenly distributed combined overloading. A 19-year-old female patient was free from any metal overloading after 7 years of treatment. Post-treatment overloading in another 6 patients ranged between evenly distributed combined patterns and isolated iron patterns. All patients had hypoceruloplasminemia throughout treatment periods. A patient with normoceruloplasminemic ICT continued to display isolated copper overloading after 2.5 years of treatment. In conclusion, these observations support the hypothesis that iron accumulates in patients with hypoceruloplasminemia.
威尔逊病(WD)是一种主要的原发性铜中毒类型,与血浆铜蓝蛋白血症相关,而特发性铜中毒(ICT)是一种以正常血浆铜蓝蛋白血症为特征的次要类型。由于血浆铜蓝蛋白是主要的循环铁氧化酶,WD患者的铁代谢可能会受到影响。从原发性铜中毒患者获取的肝脏活检标本用戊二醛溶液固定,并包埋在环氧树脂中。将已用或未用醋酸铀溶液染色的超薄切片在配备能量色散X射线分析仪的电子显微镜下进行检查。一名7岁的WD男孩在治疗前阶段没有任何金属过载情况。另外16名患者的治疗前肝脏标本显示出各种铜和铁过载模式,从孤立的铜过载到均匀分布的联合过载。一名19岁女性患者在治疗7年后没有任何金属过载情况。另外6名患者的治疗后过载情况介于均匀分布的联合模式和孤立的铁模式之间。所有患者在整个治疗期间都有血浆铜蓝蛋白血症。一名血浆铜蓝蛋白正常的ICT患者在治疗2.5年后仍持续表现出孤立的铜过载。总之,这些观察结果支持了血浆铜蓝蛋白血症患者体内铁会蓄积的假说。