Christodoulou J, Danks D M, Sarkar B, Baerlocher K E, Casey R, Horn N, Tümer Z, Clarke J T
Division of Clinical Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med Genet. 1998 Mar 5;76(2):154-64.
We report on the long-term clinical course of 4 boys with Menkes disease, treated from early infancy with parenteral copper-histidine, with follow-up over 10-20 years. Three of the 4 had male relatives with a severe clinical course compatible with classical Menkes disease. As a consequence of early treatment, our patients have normal or near-normal intellectual development, but have developed many of the more severe somatic abnormalities of the related disorder, occipital horn syndrome, including severe orthostatic hypotension in 2. In addition, 1 boy developed a previously unreported anomaly, namely, massive splenomegaly and hypersplenism as a consequence of a splenic artery aneurysm. Previously reported molecular studies in 2 of these patients had shown gene defects which would have predicted a truncated and probably nonfunctional gene product. Despite the favorable effects on the neurological symptoms, parenteral copper treatment for Menkes disease should still be regarded as experimental. The development of more effective treatments must await a more precise delineation of the role which the Menkes protein plays in intracellular copper trafficking.
我们报告了4名患有门克斯病的男孩的长期临床病程，他们从婴儿早期开始接受胃肠外铜-组氨酸治疗，并进行了10至20年的随访。这4名患者中有3名有男性亲属，其临床病程严重，与经典门克斯病相符。由于早期治疗，我们的患者智力发育正常或接近正常，但出现了相关疾病枕角综合征的许多更严重的躯体异常，其中2例出现严重的体位性低血压。此外，1名男孩出现了一种以前未报告的异常情况，即由于脾动脉瘤导致的巨大脾肿大和脾功能亢进。此前对其中2名患者进行的分子研究显示存在基因缺陷，这些缺陷原本预计会产生截短且可能无功能的基因产物。尽管胃肠外铜治疗对神经症状有良好效果，但门克斯病的胃肠外铜治疗仍应被视为实验性的。更有效治疗方法的开发必须等待对门克斯蛋白在细胞内铜转运中所起作用的更精确描述。
