Adult‐onset noncirrhotic hyperammonemia (NCH) is poorly understood and has a high morbidity and mortality. To elucidate the etiology and management of NCH, we performed a retrospective analysis of 23 adults (median age 51) with NCH treated between 2014 and 2020 at two academic medical centers. Hyperammonemia was diagnosed in all cases during the evaluation of altered mental status, with 22% presenting with seizures. Peak ammonia levels were >200 μmol/L in 70% of cases. Defects in ammonia metabolism were assessed using urea cycle biochemical testing, germline genetic testing, and testing for urease‐producing infectious agents. Ammonia metabolism defects in these cases appear attributable to four major sources: (a) infection with urease‐producing organism (n = 5); (b) previously undiagnosed inborn errors of metabolism (IEMs) (n = 4); (c) clinical exposures causing acquired urea cycle dysfunction (n = 6); and (d) unexplained acquired urea cycle dysfunction (uaUCD) (n = 8), as evidenced by biochemical signatures of urea cycle dysfunction without a genetic or clinical exposure. Severe protein malnutrition appeared to be a reversible risk factor for uaUCD. Overall, 13% of our cohort died prior to resolution of hyperammonemia, 26% died after hyperammonemia resolution, 57% survived after having reversible neurological changes, and 4% survived with irreversible neurological changes. Renal replacement therapy for ammonia clearance was often utilized for patients with an ammonia level above 250 μmol/L and patients were frequently empirically treated with antibiotics targeting urea‐splitting organisms. Our study demonstrates that acquired urea cycle dysfunction, IEMs and urease‐producing infections are major sources of adult‐onset NCH and highlights successful management strategies for adult‐onset NCH.

中文翻译：

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一项对非肝硬化高氨血症成年患者的回顾性研究。

成人发病的非肝硬化高氨血症 (NCH) 知之甚少，发病率和死亡率都很高。为了阐明 NCH 的病因和治疗，我们对 23 名在 2014 年至 2020 年期间在两个学术医疗中心接受治疗的 NCH 成人（中位年龄 51 岁）进行了回顾性分析。在评估精神状态改变的过程中，所有病例均诊断出高氨血症，其中 22% 表现为癫痫发作。在 70% 的病例中，峰值氨水平 >200 μmol/L。氨代谢缺陷通过尿素循环生化检测、种系基因检测和产脲酶感染因子检测进行评估。这些病例中的氨代谢缺陷似乎可归因于四个主要来源：（a）产生脲酶的生物体感染（n = 5）；(b) 先前未确诊的先天性代谢障碍 (IEM)（n = 4）；(c) 导致获得性尿素循环功能障碍的临床暴露（n = 6）；(d) 不明原因的获得性尿素循环功能障碍 (uaUCD)（n = 8），如无遗传或临床暴露的尿素循环功能障碍的生化特征所证明。严重的蛋白质营养不良似乎是 uaUCD 的可逆风险因素。总体而言，我们的队列中有 13% 在高氨血症消退前死亡，26% 在高氨血症消退后死亡，57% 在出现可逆神经系统变化后存活，4% 在出现不可逆神经系统变化后存活。用于氨清除的肾脏替代疗法通常用于氨水平高于 250 μmol/L 的患者，并且患者经常经验性地使用针对尿素分解生物的抗生素进行治疗。我们的研究表明，获得性尿素循环功能障碍，