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Abstract：
Urea cycle disorders (UCDs) are inherited metabolic diseases that lead to hyperammonemia with variable clinical manifestations. Using data from a nationwide study, we investigated the onset time, gene variants, clinical manifestations, and treatment of patients with UCDs in Japan. Of the 229 patients with UCDs diagnosed and/or treated between January 2000 and March 2018, identified gene variants and clinical information were available for 102 patients, including 62 patients with ornithine transcarbamylase (OTC) deficiency, 18 patients with carbamoyl phosphate synthetase 1 (CPS1) deficiency, 16 patients with argininosuccinate synthetase (ASS) deficiency, and 6 patients with argininosuccinate lyase (ASL) deficiency. A total of 13, 10, 4, and 5 variants in the OTC, CPS1, ASS, and ASL genes were respectively identified as novel variants, which were neither registered in ClinVar databases nor previously reported. The onset time and severity in patients with UCD could be predicted based on the identified gene variants in each patient from this nationwide study and previous studies. This genetic information may help in predicting the long-term outcome and determining specific treatment strategies such as liver transplantation in patients with UCDs.
摘要：
尿素循环障碍（UCD）是遗传性代谢疾病，可导致高氨血症，临床表现各不相同。利用一项全国性研究的数据，我们调查了发病时间，基因变异，临床表现，以及日本UCD患者的治疗。在2000年1月至2018年3月期间诊断和/或治疗的229例UCD患者中，有102例患者获得了已确定的基因变异和临床信息。包括62例鸟氨酸转碳淀粉酶（OTC）缺乏症患者，18例氨基甲酰磷酸合成酶1（CPS1）缺乏症患者，16例精氨酸琥珀酸合成酶（ASS）缺乏症患者，和6例精氨酸琥珀酸裂解酶（ASL）缺乏症患者。OTC中总共有13、10、4和5个变体，CPS1,ASS,和ASL基因分别被鉴定为新的变异体，既没有在ClinVar数据库中注册，也没有以前报告。UCD患者的发病时间和严重程度可以根据从这项全国性研究和先前研究中确定的每个患者的基因变异来预测。这种遗传信息可能有助于预测长期结果并确定特定的治疗策略，例如UCD患者的肝移植。
