Urea cycle disorders (UCDs) are inherited metabolic diseases causing hyperammonemia by defects in urea cycle enzymes or transporters. Liver transplantation (LT) currently is the only curative treatment option until novel therapies become available. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to investigate the effect of LT in patients with UCDs in Japan. A total of 231 patients with UCDs were enrolled in this study. Of them, a total of 78 patients with UCDs (30 male and 16 female ornithine transcarbamylase deficiency (OTCD), 21 carbamoyl phosphate synthetase 1 deficiency (CPSD), 10 argininosuccinate synthetase deficiency (ASSD) and 1 arginase 1 deficiency (ARGD)) had undergone LT. Concerning the maximum blood ammonia levels at the onset time in the transplanted male OTCD (N = 28), female OTCD (N = 15), CPSD (N = 21) and ASSD (N = 10), those were median 634 (IQR: 277-1172), 268 (211-352), 806 (535-1382), and 628 (425-957) μmol/L, respectively. The maximum blood ammonia levels in female OTCD were thus significantly lower than in the other UCDs (all P < .01). LT was effective for long-term survival, prevented recurrent hyperammonemia attack, and lowered baseline blood ammonia levels in patients with UCDs. LT had limited effect for ameliorating neurodevelopmental outcome in patients with severe disease because hyperammonemia at the onset time already had a significant impact on the brain. Patients with ASSD may be more likely to survive without cognitive impairment by receiving early LT despite severe neonatal hyperammonemia ≥ 360 μmol/L. In patients with neonatal onset OTCD or CPSD, there may be additional factors with adverse effects on the brain that are not improved by LT.

中文翻译：

---

肝移植在尿素循环障碍中的作用：来自日本一项全国性研究的报告

尿素循环障碍 (UCD) 是遗传性代谢疾病，通过尿素循环酶或转运蛋白的缺陷引起高氨血症。在新疗法出现之前，肝移植 (LT) 目前是唯一的治愈性治疗选择。我们在 2000 年 1 月至 2018 年 3 月期间进行了一项全国性的问卷调查，以调查 LT 对日本 UCD 患者的影响。本研究共招募了 231 名 UCD 患者。其中，共有 78 名 UCD 患者（30 名男性和 16 名女性鸟氨酸转氨甲酰酶缺乏症（OTCD）、21 例氨基甲酰磷酸合成酶 1 缺乏症（CPSD）、10 例精氨琥珀酸合成酶缺乏症（ASSD）和 1 例精氨酸酶 1 缺乏症（ARGD））经历了LT。关于移植的男性 OTCD (N = 28)、女性 OTCD (N = 15) 发病时的最高血氨水平，CPSD (N = 21) 和 ASSD (N = 10)，中位数为 634 (IQR: 277-1172)、268 (211-352)、806 (535-1382) 和 628 (425-957) μmol/L ， 分别。因此，女性 OTCD 的最大血氨水平显着低于其他 UCD（所有P  < .01)。LT 对长期生存有效，可防止复发性高氨血症发作，并降低 UCD 患者的基线血氨水平。LT 在改善重症患者的神经发育结果方面效果有限，因为发病时的高氨血症已经对大脑产生了显着影响。尽管严重的新生儿高氨血症≥ 360 μmol/L，但 ASSD 患者通过接受早期 LT 可能更有可能在没有认知障碍的情况下存活。在新生儿发病的 OTCD 或 CPSD 患者中，可能存在其他对大脑有不良影响的因素，而 LT 并未改善这些因素。