Department of Nutrition and Food Studies, College of Education and Human Services, Montclair State University, Montclair, NJ 07043, USA.
Department of Human Genetics, McGill University, Montreal, QC H4A 3J1, Canada.
Cells. 2022 Jun 10;11(12):1891. doi: 10.3390/cells11121891.
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.
泽尔韦格综合征（ZSD）是一种罕见的、使人衰弱的过氧化物酶体生物发生遗传疾病，影响多个器官系统，并具有广泛的临床异质性。虽然已经描述了严重、中度和轻度 ZSD 形式，但这些分类通常是任意的，这使得难以理解个体的预后和治疗效果。本研究的目的是对现有文献进行范围界定综述和荟萃分析，并对医疗记录进行回顾，以确定临床特征的描述是否可以预测 ZSD 的严重程度。我们对描述 ZSD 严重程度、临床发现和生存的文献进行了 PubMed 搜索，结果有 107 项研究（代表 307 名患者）被纳入综述和荟萃分析。我们还从我们的自然史研究中收集并分析了来自 136 名 ZSD 个体的相同参数的医疗记录。在严重程度类别中存在显著差异的常见临床发现包括癫痫发作、张力减退、活动能力降低、喂养困难、肾囊肿、肾上腺功能不全、听力和视力丧失以及寿命缩短。我们的主要数据分析还揭示了在生长不良、胃食管反流、骨折、整体发育迟缓、言语交流困难和心脏异常等严重程度类别中存在显著差异。对临床发现和非常长链脂肪酸（VLCFA）二十六烷酸（C26:0）水平进行单变量多项逻辑建模分析表明，在癫痫发作、异常脑电图、肾囊肿和心脏异常以及血浆 C26:0 脂肪酸水平中存在的临床发现数量可以区分严重程度类别。我们报告了与 ZSD 整体疾病严重程度相关的最大的临床发现特征。这些信息将有助于确定 ZSD 临床试验中特定受试者的适当结局。
