Urea cycle disorders (UCDs) are inherited metabolic disorders with impaired nitrogen detoxification caused by defects in urea cycle enzymes. They often manifest with hyperammonemic attacks resulting in significant morbidity or death. We performed a nationwide questionnaire-based study between January 2000 and March 2018 to document all UCDs in Japan, including diagnoses, treatments, and outcomes. A total of 229 patients with UCDs were enrolled in this study: 73 males and 53 females with ornithine transcarbamylase deficiency (OTCD), 33 patients with carbamoylphosphate synthetase 1 deficiency, 48 with argininosuccinate synthetase deficiency, 14 with argininosuccinate lyase deficiency, and 8 with arginase deficiency. Survival rates at 20 years of age of male and female patients with late-onset OTCD were 100% and 97.7%, respectively. Blood ammonia levels and time of onset had a significant impact on the neurodevelopmental outcome (P < .001 and P = .028, respectively). Hemodialysis and liver transplantation did not prevent poor neurodevelopmental outcomes. While treatment including medication, hemodialysis, and liver transplantation may aid in decreasing blood ammonia and/or preventing severe hyperammonemia, a blood ammonia level ≥ 360 μmol/L was found to be a significant indicator for a poor neurodevelopmental outcome. In conclusion, although current therapy for UCDs has advanced and helped saving lives, patients with blood ammonia levels ≥ 360 μmol/L at onset often have impaired neurodevelopmental outcomes. Novel neuroprotective measures should therefore be developed to achieve better neurodevelopmental outcomes in these patients.

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尿素循环障碍的长期结果：日本全国性研究报告

尿素循环障碍 (UCD) 是遗传性代谢障碍，由尿素循环酶缺陷引起的氮解毒功能受损。它们通常表现为高氨血症发作，导致严重的发病或死亡。我们在 2000 年 1 月至 2018 年 3 月期间进行了一项全国性的基于问卷调查的研究，以记录日本的所有 UCD，包括诊断、治疗和结果。本研究共纳入 229 例 UCD 患者：73 名男性和 53 名女性患有鸟氨酸转氨甲酰酶缺乏症 (OTCD)，33 名患有氨基甲酰磷酸合成酶 1 缺乏症，48 名患有精氨琥珀酸合成酶缺乏症，14 名患有精氨琥珀酸裂解酶缺乏症，8 名患有精氨酸酶不足。男性和女性迟发性 OTCD 患者 20 岁时的存活率分别为 100% 和 97.7%。P  < .001 和P  = .028，分别）。血液透析和肝移植并不能防止不良的神经发育结果。虽然包括药物治疗、血液透析和肝移植在内的治疗可能有助于降低血氨和/或预防严重的高氨血症，但血氨水平 ≥ 360 μmol/L 被发现是不良神经发育结果的重要指标。总之，尽管目前对 UCD 的治疗已取得进展并有助于挽救生命，但发病时血氨水平 ≥ 360 μmol/L 的患者通常会损害神经发育结果。因此，应开发新的神经保护措施，以在这些患者中获得更好的神经发育结果。