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GM1 gangliosidosis type II: Results of a 10-year prospective study.
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; Tifft, Cynthia J.
Afiliación
  • 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.
Genet Med ; 26(7): 101144, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38641994
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Imagen por Resonancia Magnética / Gangliosidosis GM1 Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Imagen por Resonancia Magnética / Gangliosidosis GM1 Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Genet Med Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article