INTRODUCTION Type 1 GM1 gangliosidosis is an ultra-rare, rapidly fatal lysosomal storage disorder, with life expectancy of <3 years of age. To date, only one prospective natural history study of limited size has been reported. Thus, there is a need for additional research to provide a better understanding of the progression of this disease. We have leveraged the past two decades of medical literature to conduct the first comprehensive retrospective study characterizing the natural history of Type 1 GM1 gangliosidosis. OBJECTIVES The objectives of this study were to establish a large sample of patients from the literature in order to identify: 1) clinically distinguishing factors between Type 1 and Type 2 GM1 gangliosidosis, 2) age at first symptom onset, first hospital admission, diagnosis, and death, 3) time to onset of common clinical findings, and 4) timing of developmental milestone loss. METHODS PubMed was searched with the keyword "GM1 Gangliosidosis" and for articles from the year 2000 onwards. A preliminary review of these results was conducted to establish subtype classification criteria for inclusion of only Type 1 patients, resulting in 44 articles being selected to generate the literature dataset of 154 Type 1 GM1 gangliosidosis patients. Key clinical events of these patient cases were recorded from the articles. RESULTS Comprehensive subtyping criteria for Type 1 GM1 gangliosidosis were created, and clinical events, including onset, diagnosis, death, and symptomology, were mapped over time. In this dataset, average age of diagnosis was 8.7 months, and average age of death was 18.9 months. DISCUSSION This analysis demonstrates the predictable clinical course of this disease, as almost all patients experienced significant multi-organ system dysfunction and neurodevelopmental regression, particularly in the 6- to 18-month age range. Patients were diagnosed at a late age relative to disease progression, indicating the need for improved public awareness and screening. CONCLUSION This study highlights the significant burden of illness in this disease and provides critical natural history data to drive earlier diagnosis, inform clinical trial design, and facilitate family counseling.

中文翻译：

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1型婴儿GM1神经节病的自然史：基于文献的荟萃分析。

简介1型GM1神经节苷脂病是一种罕见，快速致命的溶酶体贮积病，预期寿命小于3岁。迄今为止，仅报道了一项规模有限的前瞻性自然史研究。因此，需要进行其他研究以更好地了解该疾病的进展。我们利用了过去二十年的医学文献来进行首次全面的回顾性研究，以研究1型GM1神经节病的自然病史。目的本研究的目的是从文献中收集大量患者，以鉴定：1）临床上区分1型和2型GM1神经节病的因素，2）首次出现症状的年龄，首次住院，诊断，和死亡 3）出现常见临床发现的时间，以及4）发育里程碑丧失的时机。方法使用关键词“ GM1神经节苷脂”搜索PubMed，并搜索2000年以后的文章。对这些结果进行了初步审查，以建立仅纳入1型患者的亚型分类标准，从而选择了44篇文章来生成154位1型GM1神经节病患者的文献数据集。从文章中记录了这些患者病例的关键临床事件。结果创建了用于1型GM1神经节病的综合分型标准，并随时间绘制了包括起病，诊断，死亡和症状在内的临床事件。在此数据集中，平均诊断年龄为8.7个月，平均死亡年龄为18.9个月。讨论由于几乎所有患者都经历了明显的多器官系统功能障碍和神经发育退化，尤其是在6至18个月的年龄范围内，因此该分析证明了该疾病的可预见的临床病程。相对于疾病进展，患者被诊断为较晚年龄，这表明需要提高公众意识和筛查。结论本研究强调了该疾病的重大疾病负担，并提供了重要的自然史数据，以推动早期诊断，为临床试验设计提供信息并为家庭咨询提供便利。相对于疾病进展，患者被诊断为较晚年龄，这表明需要提高公众意识和筛查。结论本研究强调了该疾病的重大疾病负担，并提供了重要的自然史数据，以推动早期诊断，为临床试验设计提供信息并为家庭咨询提供便利。相对于疾病进展，患者被诊断为较晚年龄，这表明需要提高公众意识和筛查。结论本研究强调了该疾病的重大疾病负担，并提供了重要的自然史数据，以推动早期诊断，为临床试验设计提供信息并为家庭咨询提供便利。