可治疗ID应用程序于2012年创建,作为数字工具,旨在改善可治疗的遗传性代谢紊乱(IMD)的早期识别和干预,这些疾病具有全球发育迟缓和智力障碍(统称为“可治疗ID”)。我们的目标是更新2012年对可治疗ID和应用程序的审查,以捕获在识别新IMD方面取得的进展以及催化治疗开发和实施的病理生理学见解。
两名独立审阅者查询PubMed,OMIM和Orphanet数据库重新评估所有以前纳入的疾病和疗法,并确定2012年至2021年期间发布的所有可治疗ID报告。如果在IMD国际分类(ICIMD)中列出并以ID为主要特征,如果有发表的治疗干预措施改善ID主要和/或次要结局的证据.临床症状数据,诊断测试,治疗策略,对结果的影响,和证据水平由审稿人和外部专家提取和评估。生成的知识被翻译成诊断算法和具有新颖功能的应用程序的更新版本。
我们的审查确定了116个可治疗的ID(139个基因),其中44名新确认,属于17个ICIMD类别。最常见的治疗干预是营养,药理和维生素和微量元素补充。证据水平从1到3不等(试验,队列研究,病例对照研究)19%和4-5(病例报告,专家意见)81%的治疗。报告的效果包括62%的临床恶化改善,47%的神经系统表现和37%的发育。
我们的文献综述确定的可治疗ID的数量在八年内增加了三分之一以上。尽管基因和酶替代疗法受到了广泛的关注,大多数有效的治疗方法是营养的,相对实惠,广泛可用且(通常)令人惊讶的有效。我们提出了一个诊断算法(可调整到本地资源和专业知识)和更新的应用程序,以促进快速和准确的工作,优先考虑可治疗的ID。我们的数字工具可以作为Native和WebApp免费提供(www.treatable-id.org)具有几个新颖的功能。我们的可治疗ID努力有助于治疗代谢组和国际罕见疾病研究联盟的目标,使临床医生能够为我们的罕见疾病患者提供快速的循证干预措施。
The Treatable ID App was created in 2012 as digital tool to improve early recognition and intervention for treatable inherited metabolic disorders (IMDs) presenting with global developmental delay and intellectual disability (collectively \'treatable IDs\'). Our aim is to update the 2012
review on treatable IDs and App to capture the advances made in the identification of new IMDs along with increased pathophysiological insights catalyzing therapeutic development and implementation.
Two independent reviewers queried PubMed, OMIM and Orphanet databases to reassess all previously included disorders and therapies and to identify all reports on Treatable IDs published between 2012 and 2021. These were included if listed in the International Classification of IMDs (ICIMD) and presenting with ID as a major feature, and if published evidence for a therapeutic intervention improving ID primary and/or secondary outcomes is available. Data on clinical symptoms, diagnostic testing, treatment strategies, effects on outcomes, and evidence levels were extracted and evaluated by the reviewers and external experts. The generated knowledge was translated into a diagnostic algorithm and updated version of the App with novel features.
Our
review identified 116 treatable IDs (139 genes), of which 44 newly identified, belonging to 17 ICIMD categories. The most frequent therapeutic interventions were nutritional, pharmacological and vitamin and trace element supplementation. Evidence level varied from 1 to 3 (trials, cohort studies, case-control studies) for 19% and 4-5 (case-report, expert opinion) for 81% of treatments. Reported effects included improvement of clinical deterioration in 62%, neurological manifestations in 47% and development in 37%.
The number of treatable IDs identified by our literature
review increased by more than one-third in eight years. Although there has been much attention to gene-based and enzyme replacement therapy, the majority of effective treatments are nutritional, which are relatively affordable, widely available and (often) surprisingly effective. We present a diagnostic algorithm (adjustable to local resources and expertise) and the updated App to facilitate a swift and accurate workup, prioritizing treatable IDs. Our digital tool is freely available as Native and Web App (www.treatable-id.org) with several novel features. Our Treatable ID endeavor contributes to the Treatabolome and International Rare Diseases Research Consortium goals, enabling clinicians to deliver rapid evidence-based interventions to our rare disease patients.