■精氨酸酶1缺乏症(ARG1-D)是一种罕见的,以包括痉挛在内的临床表现为特征的进行性和衰弱性尿素循环障碍,癫痫发作,发育迟缓,智力残疾。这项系统评价的目的是确定和总结ARG1-D的自然史和患者未满足的需求。
■对已发表的病例报告进行了全面搜索,以确定ARG1-D患者,无论采取何种干预措施,比较,或结果。MEDLINE,EMBASE,Cochrane中央控制试验登记册,和其他循证医学文献数据库于2020年4月20日检索。使用JoannaBriggs研究所(JBI)关键评估清单评估质量。(PROSPERO注册:CRD42020212142。).
■111份出版物中纳入了157例ARG1-D患者(根据JBI的清单,总体质量良好);84例(53.5%)为男性。运动障碍(包括痉挛),智力残疾,>50%的病例报告了癫痫发作。诊断时的平均年龄(SD)为6.4岁,最常报道的支持诊断的实验室检查结果包括血浆精氨酸升高(81.5%)。通过基因检测ARG1基因突变(60%),和红细胞精氨酸酶活性的缺乏/降低(51%)。报告的管理方法主要包括饮食蛋白质限制(68%),氮清除剂(45%),和必需氨基酸补充剂(21%)。据作者报告,26%的患者有临床改善,15%恶化,19%的人变化有限或没有变化;特别是,40%病例未报告临床结局的指征.
这篇综述说明了严重的疾病负担,并强调了对ARG1-D患者临床有效治疗方案的相当大的未满足需求。
UNASSIGNED: Arginase 1 deficiency (ARG1-D) is a rare, progressive and debilitating urea cycle disorder characterized by clinical manifestations including spasticity, seizures, developmental delay, and intellectual disability. The aim of this systematic review was to identify and summarize the natural history of ARG1-D and the unmet needs of patients.
UNASSIGNED: A comprehensive search of published case reports was undertaken to identify patients with ARG1-D regardless of interventions, comparisons, or outcomes. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other evidence-based medicine literature databases were searched on 20 April 2020. Quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. (PROSPERO registration: CRD42020212142.).
UNASSIGNED: One hundred and fifty seven ARG1-D patients were included from 111 publications (good overall quality based on JBI\'s Checklist); 84 (53.5%) were males. Motor deficits (including spasticity), intellectual disability, and seizures were reported in >50% of the cases. Mean age (SD) at diagnosis was 6.4 years and the laboratory findings most commonly reported to support diagnosis included elevated plasma arginine (81.5%), mutation in ARG1 gene through genetic testing (60%), and absence/reduction of red blood cell arginase activity (51%). Reported management approaches mainly included dietary protein restriction (68%), nitrogen scavengers (45%), and essential amino acid supplements (21%). Author-reported clinical improvement was documented for 26% of patients, 15% deteriorated, and 19% had limited or no change; notably, no indication of clinical outcome was reported for 40% cases.
UNASSIGNED: This review illustrates a significant burden of disease and highlights a considerable unmet need for clinically effective treatment options for patients with ARG1-D.