The natural history of Type 1 infantile GM1 gangliosidosis: A literature-based meta-analysis
| Autor: | Ajith Karunakara, Cynthia J. Tifft, Frederick Lang, Paul Korner, Mark Harnett |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pediatrics medicine.medical_specialty PubMed Endocrinology Diabetes and Metabolism Disease 030105 genetics & heredity Biochemistry Article 03 medical and health sciences 0302 clinical medicine Endocrinology Rare Diseases Genetics Medicine Humans Molecular Biology Retrospective Studies Gangliosidosis GM1 business.industry Clinical study design Infant beta-Galactosidase Subtyping Natural history Lysosomal Storage Diseases Neurodevelopmental Disorders Meta-analysis Developmental Milestone Life expectancy business 030217 neurology & neurosurgery Natural history study |
| Zdroj: | Mol Genet Metab |
| ISSN: | 1096-7206 |
| Popis: | INTRODUCTION: Type 1 GM1 gangliosidosis is an ultra-rare, rapidly fatal lysosomal storage disorder, with life expectancy of less than 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 key word “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. |
| Databáze: | OpenAIRE |
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