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

Authors

• Precilla D'Souza, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Cristan Farmer, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD.
• Jean M. Johnston, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Sangwoo T. Han, Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• David Adams, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD.
• Adam L. Hartman, Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda, MD.
• Wadih Zein, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD.
• Laryssa A. Huryn, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD.
• Beth Solomon, Rehabilitation Medicine Department, Warren C. Magnuson Clinical Research Center, Bethesda, MD.
• Kelly King, Neurology Branch, National Institute on Deafness and Other Communication Disorders, Bethesda, MD.
• Christopher P. Jordan, Cardiology Department, Inova Children's Hospital, Fairfax, VA.
• Jennifer Myles, Nutrition Department, Warren C. Magnuson Clinical Research Center, Bethesda, MD.
• Elena-Raluca Nicoli, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Caroline E. Rothermel, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Yoliann Mojica Algarin, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Reyna Huang, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Rachel Quimby, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Mosufa Zainab, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Sarah Bowden, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Anna Crowell, Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD; Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD.
• Ashura Buckley, Sleep and Neurodevelopment Service, National Institute of Mental Health, Bethesda, MD.
• Carmen Brewer, Neurology Branch, National Institute on Deafness and Other Communication Disorders, Bethesda, MD.
• Debra S. Regier, Genetics and Metabolism, Children's National Hospital, Washington, DC.
• Brian P. Brooks, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD.
• Maria T. Acosta, Undiagnosed Disease Program, National Human Genome Research Institute, Bethesda, MD.
• Eva H. Baker, Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, MD.
• Gilbert Vézina, 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.
• Audrey Thurm, Neurodevelopmental and Behavioral Phenotyping Service, National Institute of Mental Health, Bethesda, MD.
• Cynthia J. Tifft, 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.

Document Type

Journal Article

Publication Date

7-1-2024

Journal

Genetics in medicine : official journal of the American College of Medical Genetics

Volume

26

Issue

7

DOI

10.1016/j.gim.2024.101144

Keywords

GM1 gangliosidosis; Late infantile; Lysosomal storage disorder; Natural history study; Type 1

Abstract

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.

APA Citation

D'Souza, Precilla; Farmer, Cristan; Johnston, Jean M.; Han, Sangwoo T.; Adams, David; Hartman, Adam L.; Zein, Wadih; Huryn, Laryssa A.; Solomon, Beth; King, Kelly; Jordan, Christopher P.; Myles, Jennifer; Nicoli, Elena-Raluca; Rothermel, Caroline E.; Mojica Algarin, Yoliann; Huang, Reyna; Quimby, Rachel; Zainab, Mosufa; Bowden, Sarah; Crowell, Anna; Buckley, Ashura; Brewer, Carmen; Regier, Debra S.; Brooks, Brian P.; Acosta, Maria T.; Baker, Eva H.; Vézina, Gilbert; Thurm, Audrey; and Tifft, Cynthia J., "GM1 gangliosidosis type II: Results of a 10-year prospective study" (2024). GW Authored Works. Paper 5391.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/5391

Department

Radiology