Quantitative longitudinal natural history of 8 gangliosidoses

• Verfasst von: Ries, Markus [VerfasserIn]
• Verfasst von: Mendoza, Grecia [VerfasserIn]
• Verfasst von: Arash-Kaps, Laila [VerfasserIn]
• Verfasst von: Amraoui, Yasmina [VerfasserIn]
• Verfasst von: Quack, Folker [VerfasserIn]
• Verfasst von: Hardt, Brigitte [VerfasserIn]
• Verfasst von: Diederich, Stefan [VerfasserIn]
• Verfasst von: Beck, Michael [VerfasserIn]
• Verfasst von: Mengel, Eugen [VerfasserIn]
• Titel: Quantitative longitudinal natural history of 8 gangliosidoses
• Titelzusatz: conceptual framework and baseline data of the German 8-in-1 disease registry : a cross-sectional analysis
• Verf.angabe: Markus Ries, Grecia Mendoza, Laila Arash-Kaps, Yasmina Amraoui, Folker Quack, Brigitte Hardt, Stefan Diederich, Michael Beck, Eugen Mengel
• E-Jahr: 2022
• Jahr: 4 October 2022
• Umfang: 10 S.
• Fussnoten: Gesehen am 05.10.2022
• Titel Quelle: Enthalten in: Genetics in medicine
• Ort Quelle: Amsterdam : Elsevier, 1998
• Jahr Quelle: 2022
• Band/Heft Quelle: 24(2022), 12, Seite 2434-2443
• ISSN Quelle: 1530-0366
• DOI: doi:10.1016/j.gim.2022.09.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: G(M1)-gangliosidosis
• Sach-SW: G(M2)-activator deficiency
• Sach-SW: Natural history
• Sach-SW: Sandhoff disease
• Sach-SW: Tay-Sachs disease
• K10plus-PPN: 1818060140

Abstract

PURPOSE: Gangliosidoses are a group of inherited neurogenetic autosomal recessive lysosomal storage disorders usually presenting with progressive macrocephaly, developmental delay, and regression, leading to significant morbidity and premature death. A quantitative definition of the natural history would support and enable clinical development of specific therapies. - METHODS: Single disease registry of 8 gangliosidoses (NCT04624789). Cross-sectional analysis of baseline data in N = 26 patients. Primary end point: disease severity assessed by the 8-in-1 score. Secondary end points: first neurologic sign or symptom observed (1) by parents and (2) by physicians, diagnostic delay, as well as phenotypical characterization. Tertiary end points: neurologic outcomes (development, ataxia, dexterity) and disability. - RESULTS: The 8-in-1 score quantitatively captured severity of disease. Parents recognized initial manifestations (startle reactions) earlier than physicians (motor developmental delay and hypotonia). Median diagnostic delay was 3.16 (interquartile range 0.69-6.25) years. In total, 8 patients presented with late-infantile phenotypes. - CONCLUSION: Data in this registry raise awareness of these rare and fatal conditions to accelerate diagnosis, inform counseling of afflicted families, define quantitative end points for clinical trials, and can serve as historical controls for future therapeutic studies. We provide further insight into the rare late-infantile phenotype for GM2-gangliosidosis. Longitudinal follow up is planned.