Kido Jun, Matsumoto Shirou, Häberle Johannes, Nakajima Yoko, Wada Yoichi, Mochizuki Narutaka, Murayama Kei, Lee Tomoko, Mochizuki Hiroshi, Watanabe Yoriko, Horikawa Reiko, Kasahara Mureo, Nakamura Kimitoshi
Department of Pediatrics, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
University Children's Hospital Zurich and Children's Research Centre, Zurich, Switzerland.
J Inherit Metab Dis. 2021 Jul;44(4):826-837. doi: 10.1002/jimd.12384. Epub 2021 Apr 18.
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.
尿素循环障碍（UCDs）是遗传性代谢障碍，因尿素循环酶缺陷导致氮解毒受损。它们常表现为高氨血症发作，可导致严重发病或死亡。我们在2000年1月至2018年3月期间开展了一项全国性问卷调查研究，以记录日本所有的尿素循环障碍病例，包括诊断、治疗及转归情况。本研究共纳入229例尿素循环障碍患者：73例男性和53例女性患有鸟氨酸转氨甲酰酶缺乏症（OTCD），33例患者患有氨甲酰磷酸合成酶1缺乏症，48例患有精氨琥珀酸合成酶缺乏症，14例患有精氨琥珀酸裂解酶缺乏症，8例患有精氨酸酶缺乏症。迟发性OTCD的男性和女性患者20岁时的生存率分别为100%和97.7%。血氨水平和发病时间对神经发育结局有显著影响（分别为P＜0.001和P = 0.028）。血液透析和肝移植并不能预防不良的神经发育结局。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水平和/或预防严重高氨血症，但发现血氨水平≥360 μmol/L是神经发育不良结局的一个重要指标。总之，尽管目前针对尿素循环障碍的治疗已有进展并有助于挽救生命，但发病时血氨水平≥360 μmol/L的患者往往存在神经发育受损的结局。因此，应开发新的神经保护措施，以使这些患者获得更好的神经发育结局。
