GM1 gangliosidosis type II: Results of a 10-year prospective study.

Autor:	D'Souza P; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Farmer C; Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD., Johnston JM; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Han ST; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Adams D; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD., Hartman AL; Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD., Zein W; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD., Huryn LA; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD., Solomon B; Rehabilitation Medicine Department, Warren C. Magnuson Clinical Research Center, Bethesda, MD., King K; Neurology Branch, National Institute on Deafness and Other Communication Disorders, Bethesda, MD., Jordan CP; Cardiology Department, Inova Children's Hospital, Fairfax, VA., Myles J; Nutrition Department, Warren C. Magnuson Clinical Research Center, Bethesda, MD., Nicoli ER; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Rothermel CE; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Mojica Algarin Y; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Huang R; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Quimby R; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Zainab M; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Bowden S; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Crowell A; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD., Buckley A; Sleep and Neurodevelopment Service, National Institute of Mental Health, Bethesda, MD., Brewer C; Neurology Branch, National Institute on Deafness and Other Communication Disorders, Bethesda, MD., Regier DS; Genetics and Metabolism, Children's National Hospital, Washington, DC., Brooks BP; Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD., Acosta MT; Undiagnosed Disease Program, National Human Genome Research Institute, Bethesda, MD., Baker EH; Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, MD., Vézina G; Program in Neuroradiology and Program in Radiology, Children's National Hospital, Washington, DC; Radiology and Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC., Thurm A; Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD., Tifft CJ; Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD. Electronic address: cynthia.tifft@nih.gov.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 Jul; Vol. 26 (7), pp. 101144. Date of Electronic Publication: 2024 Apr 16.
DOI:	10.1016/j.gim.2024.101144
Abstrakt:	Purpose: GM1 gangliosidosis (GM1) a lysosomal disorder caused by pathogenic variants in GLB1, is characterized by relentless neurodegeneration. There are no approved treatments. Methods: Forty-one individuals with type II (late-infantile and juvenile) GM1 participated in a single-site prospective observational study. Results: Classification of 37 distinct variants using American College of Medical Genetics and Genomics criteria resulted in the upgrade of 6 and the submission of 4 new variants. In contrast to type I infantile disease, children with type II had normal or near normal hearing and did not have cherry-red maculae or hepatosplenomegaly. Some older children with juvenile onset disease developed thickened aortic and/or mitral valves. Serial magnetic resonance images demonstrated progressive brain atrophy, more pronounced in late infantile patients. Magnetic resonance spectroscopy showed worsening elevation of myo-inositol and deficit of N-acetyl aspartate that were strongly correlated with scores on the Vineland Adaptive Behavior Scale, progressing more rapidly in late infantile compared with juvenile onset disease. Conclusion: Serial phenotyping of type II GM1 patients expands the understanding of disease progression and clarifies common misconceptions about type II patients; these are pivotal steps toward more timely diagnosis and better supportive care. The data amassed through this 10-year effort will serve as a robust comparator for ongoing and future therapeutic trials. Competing Interests: Conflict of Interest Adam L. Hartman receives consulting fees from Teladoc. All other authors declare no conflicts of interest. (Published by Elsevier Inc.)
Databáze:	MEDLINE
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