den Hollander Bibiche, Hoytema van Konijnenburg Eva M M, Hewitson Brittany, van der Meijden Jan C, Balfoort Berith M, Winter Brad, Müller Annelieke R, Wasserman Wyeth W, Ferreira Carlos R, van Karnebeek Clara D
Department of Pediatrics, Emma Children's Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.
Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, The Netherlands.
J Inherit Metab Dis. 2025 Jan;48(1):e12835. doi: 10.1002/jimd.12835.
Inborn errors of metabolism (IEMs) are rare genetic conditions with significant morbidity and mortality. Technological advances have increased therapeutic options, making it challenging to remain up to date. A centralized therapy knowledgebase is needed for early diagnosis and targeted treatment. This study aimed to identify all treatable IEMs through a scoping literature review, followed by data extraction and analysis according to the Treatabolome principles. Knowledge of treatable IEMs, therapeutic categories, efficacy, and evidence was integrated into the Inborn Errors of Metabolism Knowledgebase (IEMbase), an online database encompassing all IEMs. The study identified 275 treatable IEMs, 18% of all currently known 1564 IEMs, according to the International Classification of Inherited Metabolic Disorders. Disorders of fatty acid and ketone body metabolism had the highest treatability (67%), followed by disorders of vitamin and cofactor metabolism (60%), and disorders of lipoprotein metabolism (42%). The most common treatment strategies were pharmacological therapy (34%), nutritional therapy (34%), and vitamin and trace element supplementation (12%). Treatment effects were most commonly observed in nervous system abnormalities (34%), metabolism/homeostasis abnormalities (33%), and growth (7%). Predominant evidence sources included case reports with evidence levels 4 (48%) and 5 (12%), and individual cohort studies with evidence level 2b (12%). Our study generated the Metabolic Treatabolome 2024. IEMs are the largest group of monogenic disorders amenable to disease-modifying therapy. With drug repurposing efforts and advancements in gene therapies, this number will expand. IEMbase now provides up-to-date, comprehensive information on clinical and biochemical symptoms and therapeutic options, empowering patients, families, healthcare professionals, and researchers in improving patient outcomes.
先天性代谢缺陷（IEMs）是一类罕见的遗传疾病，具有较高的发病率和死亡率。技术进步增加了治疗选择，跟上最新进展颇具挑战。需要一个集中的治疗知识库来进行早期诊断和靶向治疗。本研究旨在通过范围界定文献综述识别所有可治疗的IEMs，然后根据代谢组学原则进行数据提取和分析。可治疗IEMs的知识、治疗类别、疗效和证据被整合到先天性代谢缺陷知识库（IEMbase）中，这是一个涵盖所有IEMs的在线数据库。根据《国际遗传性代谢疾病分类》，该研究识别出275种可治疗的IEMs，占目前已知的1564种IEMs的18%。脂肪酸和酮体代谢紊乱的可治疗性最高（67%），其次是维生素和辅因子代谢紊乱（60%）以及脂蛋白代谢紊乱（42%）。最常见的治疗策略是药物治疗（34%）、营养治疗（34%）以及维生素和微量元素补充（12%）。治疗效果最常出现在神经系统异常（34%）、代谢/内环境稳定异常（33%）和生长方面（7%）。主要的证据来源包括证据水平为4（48%）和5（12%）的病例报告，以及证据水平为2b（12%）的个体队列研究。我们的研究生成了《2024年代谢组学治疗》。IEMs是最适合进行疾病修饰治疗的单基因疾病群体。随着药物重新利用的努力和基因治疗的进展，这个数字将会扩大。IEMbase现在提供了关于临床和生化症状以及治疗选择的最新、全面信息，有助于患者、家庭、医疗保健专业人员和研究人员改善患者预后。
