Emory University School of Medicine, 101 Woodruff Circle, 7th Floor Suite 7130, 30322, Atlanta, GA, USA.
Children's University Hospital of Quebec, Quebec, QC, Canada.
Orphanet J Rare Dis. 2024 Apr 18;19(1):168. doi: 10.1186/s13023-024-03167-0.
The autosomal recessive disorder N-acetylglutamate synthase (NAGS) deficiency is the rarest defect of the urea cycle, with an incidence of less than one in 2,000,000 live births. Hyperammonemic crises can be avoided in individuals with NAGS deficiency by the administration of carbamylglutamate (also known as carglumic acid), which activates carbamoyl phosphatase synthetase 1 (CPS1). The aim of this case series was to introduce additional cases of NAGS deficiency to the literature as well as to assess the role of nutrition management in conjunction with carbamylglutamate therapy across new and existing cases.
We conducted retrospective chart reviews of seven cases of NAGS deficiency in the US and Canada, focusing on presentation, diagnosis, medication management, nutrition management, and outcomes.
Five new and two previously published cases were included. Presenting symptoms were consistent with previous reports. Diagnostic confirmation via molecular testing varied in protocol across cases, with consecutive single gene tests leading to long delays in diagnosis in some cases. All patients responded well to carbamylglutamate therapy, as indicated by normalization of plasma ammonia and citrulline, as well as urine orotic acid in patients with abnormal levels at baseline. Although protein restriction was not prescribed in any cases after carbamylglutamate initiation, two patients continued to self-restrict protein intake. One patient experienced two episodes of hyperammonemia that resulted in poor long-term outcomes. Both episodes occurred after a disruption in access to carbamylglutamate, once due to insurance prior authorization requirements and language barriers and once due to seizure activity limiting the family's ability to administer carbamylglutamate.
Follow-up of patients with NAGS deficiency should include plans for illness and for disruption of carbamylglutamate access, including nutrition management strategies such as protein restriction. Carbamylglutamate can help patients with NAGS deficiency to liberalize their diets, but the maximum safe level of protein intake to prevent hyperammonemia is not yet known. Patients using this medication should still monitor their diet closely and be prepared for any disruptions in medication access, which might require immediate dietary adjustments or medical intervention to prevent hyperammonemia.
常染色体隐性遗传疾病 N-乙酰谷氨酸合酶（NAGS）缺乏症是尿素循环中最罕见的缺陷，发病率低于每 200 万活产儿一例。通过给予氨甲酰谷氨酸（也称为卡谷氨酸），可以避免 NAGS 缺乏症个体发生高氨血症危象，氨甲酰谷氨酸可激活氨甲酰磷酸合成酶 1（CPS1）。本病例系列的目的是向文献中介绍更多 NAGS 缺乏症的病例，并评估在新的和现有的病例中，联合氨甲酰谷氨酸治疗进行营养管理的作用。
我们对美国和加拿大的 7 例 NAGS 缺乏症病例进行了回顾性图表审查，重点关注表现、诊断、药物管理、营养管理和结果。
纳入了 5 例新病例和 2 例已发表的病例。临床表现与以往报道一致。通过分子检测进行的诊断确认在病例之间的方案各不相同，在某些病例中，连续进行单基因检测导致诊断延迟很长时间。所有患者对氨甲酰谷氨酸治疗反应良好，表现为血浆氨和瓜氨酸正常，以及基线时尿液乳清酸异常的患者乳清酸正常。尽管在开始氨甲酰谷氨酸治疗后，没有任何病例规定限制蛋白质摄入，但有 2 例患者继续自行限制蛋白质摄入。有 1 例患者发生了 2 次高氨血症发作，导致预后不良。这两起发作都发生在氨甲酰谷氨酸获取中断之后，一次是由于保险事先授权要求和语言障碍，一次是由于癫痫发作限制了家属给药能力。
NAGS 缺乏症患者的随访应包括疾病和氨甲酰谷氨酸获取中断的计划，包括营养管理策略，如限制蛋白质摄入。氨甲酰谷氨酸可以帮助 NAGS 缺乏症患者自由饮食，但预防高氨血症的最大安全蛋白质摄入量尚不清楚。使用这种药物的患者仍应密切监测饮食，并为药物获取中断做好准备，这可能需要立即进行饮食调整或医疗干预，以预防高氨血症。
