Matalon R, Michals K, Kaul R
Research Institute, Miami Children's Hospital, Fl 33155-3009, USA.
J Pediatr. 1995 Oct;127(4):511-7. doi: 10.1016/s0022-3476(95)70105-2.
Establishing the basic defect in Canavan disease has led to reliable biochemical methods for the diagnosis of this disease. The isolation of the gene and identification of mutations causing Canavan disease have led to the possibility of using DNA methods for the diagnosis of Canavan disease and for carrier detection. A surprising finding is the high carrier frequency of this gene defect among Ashkenazi Jewish people. Analysis for two mutations leads to the identification of 97% of Jewish patients with Canavan disease, and screening of Ashkenazi Jews is possible. N-Acetylaspartic acid has been considered to be an inert compound. The pathophysiology of Canavan disease links lack of NAA hydrolysis to a severe, debilitating white matter disease. Currently, NAA is being studied in many other brain disorders, such as Alzheimer disease, Huntington disease, and stroke. However, the only disease with a specific defect in the metabolism of NAA is Canavan disease. An animal model for Canavan disease is needed to study some of the questions regarding the role of NAA in brain tissue, and for the study of therapeutic modalities, including gene therapy.
明确卡纳万病的基本缺陷后，已形成了用于诊断该疾病的可靠生化方法。卡纳万病致病基因的分离及突变鉴定，使得利用DNA方法诊断卡纳万病及检测携带者成为可能。一个惊人的发现是，这种基因缺陷在德系犹太人中的携带者频率很高。对两种突变进行分析可识别出97%的患有卡纳万病的犹太患者，对德系犹太人进行筛查成为可能。N-乙酰天门冬氨酸曾被认为是一种惰性化合物。卡纳万病的病理生理学将缺乏NAA水解与一种严重的、使人衰弱的白质疾病联系起来。目前，正在许多其他脑部疾病中研究NAA，如阿尔茨海默病、亨廷顿病和中风。然而，唯一在NAA代谢方面存在特定缺陷的疾病是卡纳万病。需要建立卡纳万病的动物模型，以研究一些关于NAA在脑组织中的作用的问题，以及用于研究包括基因治疗在内的治疗方式。
