The juvenile gangliosidoses: A timeline of clinical change

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The gangliosidoses are rare inherited diseases that result in pathologic accumulation of gangliosides in the central nervous system and other tissues, leading to severe and progressive neurological impairment and early death in the childhood forms. No treatments are currently approved for the gangliosidoses, and development of treatments is impaired by limited understanding of the natural history of these diseases. Objective: The objective of this study is to improve understanding of the juvenile gangliosidoses phenotypes and the late-infantile phenotypic subtype. Methods: Through a prospective natural history study of subjects with juvenile GM1- and GM2-gangliosidosis, a timeline of clinical changes was developed for the classic juvenile phenotypes and the late-infantile phenotypes and results of serial neurodevelopmental testing was analyzed. Results: Several candidate ‘outcome measures’ were identified: changes in ambulation and verbalization skills, the communication domain from neurodevelopmental testing and the caregiver-reported socialization domain. Conclusions: The most common symptoms leading caregivers to seek a genetic diagnosis were changes in ambulation and verbalization.

Original languageEnglish (US)
Article number100676
JournalMolecular Genetics and Metabolism Reports
Volume25
DOIs
StatePublished - Dec 2020

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health through the Lysosomal Disease Network ( U54NS065768 ). The Lysosomal Disease Network ( U54NS065768 ) is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Funding Information:
The authors thank the children and their parents and caregivers for participation as the subjects of this long term longitudinal natural history study. This work was supported by the National Institutes of Health through the Lysosomal Disease Network ( U54NS065768 ). The Lysosomal Disease Network ( U54NS065768 ) is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network (RDCRN) , supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Assistance with statistical analyses, graphics, and formatting of the final manuscript was provided by Julie Harriague, pH.D., (4Clinics, Paris, France funded by Lysogene, Paris, France).

Keywords

  • Adolescent
  • Child
  • Disease progression
  • GM1-gangliosidosis
  • Inherited metabolic diseases
  • Tay-Sachs disease

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