Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment.
Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment.
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DOI：
10.2174/138920012799320455
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发表时间：
2012-03
影响因子：
2.3
通讯作者：
Bhadhprasit W
中科院分区：
文献类型：
--
作者：
Kodama H;Fujisawa C;Bhadhprasit W
铜是所有生物体所需的必需微量元素。然而，过量的铜会导致细胞损伤。正常铜稳态的破坏是三种遗传疾病的标志：门克斯病，枕角综合征和威尔逊病。 门克斯病和枕角综合征的特点是铜缺乏。门克斯病的典型特征是铜依赖性酶活性低。标准治疗包括组氨酸铜的胃肠外给药。如果在2个月大之前开始治疗，可以预防神经变性，而延迟治疗则完全无效。因此，应开展新生儿筛查。同时，铜-组氨酸治疗不能改善结缔组织疾病。正在研究组氨酸铜注射液和口服双硫仑的联合治疗。枕角综合征以结缔组织异常为特征，是门克斯病最温和的形式。尚未对该综合征进行治疗。肝豆状核变性的特征是铜中毒，通常会严重影响肝脏和神经系统。也有其他症状，但早期诊断有时很困难。螯合剂和锌是有效的治疗方法，但对大多数暴发性肝衰竭患者无效。此外，一些患有神经性威尔逊病的患者对螯合剂的反应恶化或表现出不良反应。由于早期治疗至关重要，因此应在婴儿中实施威尔逊病的筛查系统。肝豆状核变性患者可能有发生肝细胞癌的风险。了解肝豆状核变性和肝细胞癌之间的联系将有利于疾病的治疗和预防。
Copper is an essential trace element required by all living organisms. Excess amounts of copper, however, results in cellular damage. Disruptions to normal copper homeostasis are hallmarks of three genetic disorders: Menkes disease, occipital horn syndrome, and Wilson’s disease. Menkes disease and occipital horn syndrome are characterized by copper deficiency. Typical features of Menkes disease result from low copper-dependent enzyme activity. Standard treatment involves parenteral administration of copper-histidine. If treatment is initiated before 2 months of age, neurodegeneration can be prevented, while delayed treatment is utterly ineffective. Thus, neonatal mass screening should be implemented. Meanwhile, connective tissue disorders cannot be improved by copper-histidine treatment. Combination therapy with copper-histidine injections and oral administration of disulfiram is being investigated. Occipital horn syndrome characterized by connective tissue abnormalities is the mildest form of Menkes disease. Treatment has not been conducted for this syndrome. Wilson’s disease is characterized by copper toxicity that typically affects the hepatic and nervous systems severely. Various other symptoms are observed as well, yet its early diagnosis is sometimes difficult. Chelating agents and zinc are effective treatments, but are inefficient in most patients with fulminant hepatic failure. In addition, some patients with neurological Wilson’s disease worsen or show poor response to chelating agents. Since early treatment is critical, a screening system for Wilson’s disease should be implemented in infants. Patients with Wilson’s disease may be at risk of developing hepatocellular carcinoma. Understanding the link between Wilson’s disease and hepatocellular carcinoma will be beneficial for disease treatment and prevention.
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影响因子：
25.7
作者：
Brewer, GJ;Askari, FK
通讯作者：
Askari, FK
影响因子：
30.8
作者：
BULL, PC;THOMAS, GR;COX, DW
通讯作者：
COX, DW
影响因子：
6.7
作者：
Ferenci, P;Caca, K;Berr, F
通讯作者：
Berr, F
DOI：
10.1097/00005072-196610000-00001
发表时间：
1966-01-01
影响因子：
3.2
作者：
AGUILAR, MJ;CHADWICK, DL;OKUYAMA, K
通讯作者：
OKUYAMA, K
影响因子：
4.7
作者：
Fryer, Michael J.
通讯作者：
Fryer, Michael J.