Zellweger谱系障碍(ZSD)是一种罕见的,影响多个器官系统并表现出广泛的临床异质性的过氧化物酶体生物发生衰弱的遗传性疾病。虽然严重,中间,已经描述了轻度形式的ZSD,这些名称通常是任意的,在理解个体预后和治疗有效性方面存在困难。这项研究的目的是对现有文献和医学图表进行范围审查和荟萃分析,以确定临床发现的特征是否可以预测ZSD的严重程度。我们的PubMed搜索描述严重性的文章,临床发现,ZSD的生存率导致107项研究(代表307例患者)被纳入综述和荟萃分析.我们还从自然史研究的136名ZSD个体的医疗记录中收集并分析了这些相同的参数。不同严重程度的常见临床发现包括癫痫发作,低张力,流动性降低,喂养困难,肾囊肿,肾上腺功能不全,听力和视力丧失,寿命缩短。我们的主要数据分析还显示,在未能茁壮成长的严重程度类别中,胃食管反流,骨折,全球发育迟缓,言语交际困难,和心脏异常。临床发现和超长链脂肪酸(VLCFA)六烷酸(C26:0)水平的单变量多项逻辑模型分析显示,癫痫发作中出现的临床发现数量,脑电图异常,肾囊肿,心脏异常,以及血浆C26:0脂肪酸水平可以区分严重程度类别。我们报告了与ZSD总体疾病严重程度相关的最大临床表现。该信息将有助于确定ZSD临床试验中特定受试者的适当结果。
Zellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, presenting difficulty in understanding individual prognosis and treatment effectiveness. The purpose of this study is to conduct a scoping
review and meta-analysis of existing literature and a medical chart
review to determine if characterization of clinical findings can predict severity in ZSD. Our PubMed search for articles describing severity, clinical findings, and survival in ZSD resulted in 107 studies (representing 307 patients) that were included in the
review and meta-analysis. We also collected and analyzed these same parameters from medical records of 136 ZSD individuals from our natural history study. Common clinical findings that were significantly different across severity categories included seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and a shortened lifespan. Our primary data analysis also revealed significant differences across severity categories in failure to thrive, gastroesophageal reflux, bone fractures, global developmental delay, verbal communication difficulties, and cardiac abnormalities. Univariable multinomial logistic modeling analysis of clinical findings and very long chain fatty acid (VLCFA) hexacosanoic acid (C26:0) levels showed that the number of clinical findings present among seizures, abnormal EEG, renal cysts, and cardiac abnormalities, as well as plasma C26:0 fatty acid levels could differentiate severity categories. We report the largest characterization of clinical findings in relation to overall disease severity in ZSD. This information will be useful in determining appropriate outcomes for specific subjects in clinical trials for ZSD.