In 2000 and 2001, we described factors that lead to the phenotypes of individuals with "simple," "single" gene disorders, like inherited metabolic disorders, being complex, multi-genic traits. These factors include functional thresholds, genetic and environmental modifiers, and systems dynamics, encompassing metabolic control analysis and scale-free, hub-and-spoke networks. This mini-review will consider topics influencing complexity developed in the ensuing nearly two decades, such as "synergistic heterozygosity" and "moonlighting proteins." There will be a focus on the value of the measurement of flux in evaluating the metabolome to ascertain phenotypic variability and the potential role of the gut microbiome in metabolomic flux. A point-of-care metabolomics tool, under development to improve the real time, inter-operative ascertainment of tumor margins and similar devices, will provide opportunities to improve acute care and ongoing management of individuals with inherited metabolic disorders.

中文翻译：

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代谢物通量：遗传性代谢紊乱作为复杂性状的动态概念。

在2000年和2001年，我们描述了导致具有“简单”，“单一”基因疾病（如遗传性代谢疾病）的患者的表型的因素，这些疾病是复杂的多基因性状。这些因素包括功能性阈值，遗传和环境修饰剂以及系统动力学，包括代谢控制分析和无标度，轮辐式网络。这份小型评论将考虑影响随后二十年发展起来的复杂性的主题，例如“协同杂合性”和“月光照蛋白”。在评估代谢组以确定表型变异性以及肠道微生物组在代谢组学通量中的潜在作用方面，将重点关注通量测量的价值。正在开发的即时护理代谢组学工具，可改善实时性，