BACKGROUND Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. METHODS We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. RESULTS For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. CONCLUSIONS Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies.

中文翻译：

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儿科研究中链酰基辅酶A脱氢酶（MCAD）缺乏症和苯丙酮尿症（PKU）的结果：综述。

背景技术遗传代谢疾病（IMD）是一组个别罕见的单基因疾病。对于许多IMD而言，缺乏评估临床干预效果的高质量证据。IMD干预措施的临床有效性试验可以通过开发核心结果集（COSs），建议的最小化的标准化，高质量结果集和相关结果测量工具得到支持，所有研究都应将其纳入研究领域。我们通过审查已发表的文献来描述作者报告的结果，确定研究中结果的异质性并组装出两个IMD，即中链酰基辅酶A脱氢酶（MCAD）缺乏症和苯丙酮尿症（PKU），来建立儿童COS。候选结果列表。方法我们使用了一种全面的搜索策略来识别与MCAD缺乏和PKU患儿相关的基础研究和指南，从符合条件的研究中提取研究特征和结果信息，包括用于选择结果的结果测量工具。在已建立的框架和先前发布的儿科COS的通知下，结果分为五个相互排斥的先验核心领域：增长与发展，生命影响，病理生理表现，资源利用和死亡。结果对于MCAD缺乏症，我们从52篇文章中鉴定出83种结果。最常见的核心区域是病理生理表现，在29/52篇文章中报告了33项结果（占56％）。死亡是最常报告的结局。一项研究报告了三分之一的结果。测量结果最多样化的是认知和智力/智商，在14篇文章中报告了八种独特的测量工具。对于北大，我们从343篇文章中确定了97个结果。最常代表的核心区域是病理生理表现，在281/343文章中报道了31项结果（占82％）。苯丙氨酸浓度是最常报告的结果。一项研究报告了16％的结果。与MCAD缺乏症相似，PKU结果最多样化的测量是认知和智力/智商，在82篇文章中报道了39种不同的仪器。结论在已发表的有关MCAD缺乏症和PKU的研究中，报告的结果和结果测量工具的异质性凸显了这些疾病对COS的需求，