Gene Therapy Program, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Genet Metab. 2012 Feb;105(2):263-5. doi: 10.1016/j.ymgme.2011.10.016. Epub 2011 Nov 7.
A 66 year old woman who is a manifesting heterozygote for ornithine transcarbamylase deficiency (OTCD) presented with hepatocellular carcinoma (HCC). Fourteen years prior to this presentation she participated in a phase I gene therapy study which used an adenoviral vector, thought to be non-oncogenic, to deliver a normal OTC gene to hepatocytes [1]. A recent review of data collected through a national longitudinal study of individuals with urea cycle defects [2,3] suggests that early urea cycle disorders (UCDs) are associated with hepatocellular damage and liver dysfunction in many cases. This may predispose an affected individual to a substantially increased risk of developing HCC, as has been observed in certain other inborn errors of metabolism. We speculate that the underlying urea cycle defect may be the cause of HCC in this individual.
一位 66 岁的女性，是鸟氨酸氨甲酰基转移酶缺陷症（OTCD）的表现型杂合子，患有肝细胞癌（HCC）。在本次发病前 14 年，她参加了一项 I 期基因治疗研究，该研究使用腺病毒载体（被认为是非致癌的）将正常的 OTC 基因递送到肝细胞[1]。最近对通过国家尿素循环缺陷个体纵向研究收集的数据进行的一项综述[2,3]表明，早期尿素循环障碍（UCD）在许多情况下与肝细胞损伤和肝功能障碍有关。这可能使受影响的个体面临 HCC 发展的风险大大增加，就像在某些其他先天性代谢错误中观察到的那样。我们推测该个体的 HCC 是由潜在的尿素循环缺陷引起的。
