Yokota Kazuhiro, Ohtake Akira, Yamazaki Taro, Tsuzuki-Wada Takuma, Saito-Tsuruoka Megumi, Fushimi Takuya, Murayama Kei, Akiyama Yuji, Mimura Toshihide
Department of Rheumatology and Applied Immunology, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
Department of Pediatrics, Faculty of Medicine, Saitama Medical University, Saitama, Japan.
Mol Genet Metab Rep. 2025 Mar 5;43:101200. doi: 10.1016/j.ymgmr.2025.101200. eCollection 2025 Jun.
Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM#237300) is a rare inherited disorder due to complete or partial lack of the CPS1 enzyme. Polymyositis is a relatively rare systemic inflammatory autoimmune disease. Here, we report a 59-year-old Japanese woman diagnosed with late-onset CPS1 deficiency during polymyositis treatment. The polymyositis appeared two years before the diagnosis of CPS1 deficiency. Prednisolone (PSL) at 35 mg/day initial dosage, promptly alleviated the symptoms. However, the patient, without apparent cause, suddenly developed confusion progressing to unconsciousness and coma. Upon admission, the patient's plasma ammonia levels were 458 μg/dL (269 μM). Plasma amino acid analysis revealed decreased citrulline levels and elevated glutamine levels. Genetic analysis of (OMIM *608307) showed homozygosity for the likely pathogenic variant c.2397G > A (p.Met799Ile), leading to the diagnosis of CPS1 deficiency. The patient responded to pharmacotherapy and continuous hemodialysis. However, the patient experienced hyperammonemia decompensation events while on pharmacotherapy at home, which were successfully managed with emergency treatment and/or hemodialysis. Subsequently, after liver transplantation, the patient's plasma ammonia levels consistently remained at normal. This case illustrates late-onset CPS1 deficiency manifested in an adult treated with PSL for polymyositis, and the cure of its enzyme deficiency by live-donor liver transplantation.
氨甲酰磷酸合成酶1（CPS1）缺乏症（OMIM#237300）是一种罕见的遗传性疾病，由于完全或部分缺乏CPS1酶所致。多发性肌炎是一种相对罕见的系统性炎症性自身免疫性疾病。在此，我们报告一名59岁的日本女性，在治疗多发性肌炎期间被诊断为迟发性CPS1缺乏症。多发性肌炎在CPS1缺乏症诊断前两年出现。初始剂量为35mg/天的泼尼松龙（PSL）迅速缓解了症状。然而，患者无明显诱因突然出现意识模糊，进而发展为昏迷。入院时，患者血浆氨水平为458μg/dL（269μM）。血浆氨基酸分析显示瓜氨酸水平降低，谷氨酰胺水平升高。对（OMIM *608307）的基因分析显示，可能的致病变异c.2397G>A（p.Met799Ile）呈纯合状态，从而诊断为CPS1缺乏症。患者对药物治疗和持续血液透析有反应。然而，患者在家中接受药物治疗时发生了高氨血症失代偿事件，通过紧急治疗和/或血液透析成功处理。随后，在活体供肝肝移植后，患者的血浆氨水平一直保持正常。本病例说明了在接受PSL治疗多发性肌炎的成人中表现出的迟发性CPS1缺乏症，以及通过活体供肝肝移植治愈其酶缺乏症。
