Grompe M
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Semin Liver Dis. 2001 Nov;21(4):563-71. doi: 10.1055/s-2001-19035.
The topic of this review is hepatorenal tyrosinemia (hereditary tyrosinemia type 1 [HT1], or fumarylacetoacetate hydrolase deficiency; OMIM# 276700). HT1 is the most serious and common of the genetic defects in tyrosine degradation. In addition, this disorder has importance as a model of spontaneous self-correction of liver disease, as a model of liver repopulation by transplanted cells and gene therapy, and as a genetic cause of hepatocarcinoma. However, other forms of hypertyrosinemia exist; hence, the differential diagnosis also will be described briefly. Recent years have seen much progress in our understanding of the molecular basis, the pathophysiology, and especially the treatment of HT1. The current intervention with 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC) therapy has improved the outcome of this once devastating disorder. The successful repopulation of the HT1 liver with transplanted cells and positive results in the use of gene therapy in animal models may someday lead to therapy in humans that will obviate the need for life-long dietary and pharmacological therapy.
本综述的主题是肝肾型酪氨酸血症（遗传性1型酪氨酸血症[HT1]，即延胡索酰乙酰乙酸水解酶缺乏症；OMIM#276700）。HT1是酪氨酸降解遗传缺陷中最严重且最常见的一种。此外，这种疾病作为肝病自发自我纠正的模型、移植细胞肝再生和基因治疗的模型以及肝癌的遗传病因具有重要意义。然而，还存在其他形式的高酪氨酸血症；因此，也将简要描述鉴别诊断。近年来，我们对HT1的分子基础、病理生理学，尤其是治疗方面的认识有了很大进展。目前使用2-(2-硝基-4-三氟甲基苄基)-1,3-环己二酮（NTBC）进行的干预治疗改善了这种曾经具有毁灭性疾病的治疗效果。用移植细胞成功使HT1肝脏重新细胞化以及在动物模型中基因治疗取得的阳性结果，可能有朝一日会为人类带来无需终身饮食和药物治疗的疗法。
