Similarities and differences in the late-onset GM2 gangliosidoses: Tay-Sachs and Sandhoff diseases.
Overview
- Office of the Clinical Director, National Human Genome Research Institute, Bethesda, MD 20892 USA
- Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892 USA
- Neurorehabilitation and Biomechanics Research Section, National Institutes of Health Clinical Center, Bethesda, MD USA
- ABBEL Research Division, Rehabilitation Institute at Sinai (Formerly Sinai Rehabilitation Center), Sinai Hospital, Baltimore, MD USA
- Electromyography Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD USA
Abstract
Due to shared ß-hexosamindase A deficiencies and significant clinical overlap, the predominating subtypes of late-onset GM2 gangliosidosis, late-onset Tay-Sachs (LOTS) and late-onset Sandhoff disease (LOSD) have been considered essentially indistinguishable. However, growing evidence supports several distinctions between the two entities. We highlight these distinctions through the cross-sectional evaluation of 27 (21 LOTS and 6 LOSD) late-onset GM2 gangliosidosis participants. Study protocol included physical examinations, assessments of gait, balance, muscle strength, ataxia, and nerve conduction velocities, and brain magnetic resonance imaging. Lower limb weakness and later development of upper limb weakness was highly prevalent in both diseases. Accompanying gait disturbances, balance issues, and dysmetria were also prevalent in both cohorts. Strength evaluations showed weakness in both the LOTS and LOSD cohorts compared to controls primarily impacting extensor muscles. In contrast, BARS scores for dysarthria and oculomotor dysfunction were present and heterogenous in LOTS participants and absent in LOSD participants. Twenty-four percent of LOTS participants and none of the LOSD participants had a history of neuropsychiatric symptoms. Cerebellar volume including lobules V and VI were lower in LOTS compared to LOSD and normative data. However, severe length-dependent sensory neuropathy was present in all LOSD participants but not in LOTS participants. The finding of lower cerebellar volume in LOTS suggests the distinctive features of the LOTS phenotype are related to cerebellar dysfunction. However, the cause of the phenotypic differences between LOTS and LOSD remains a mystery, and the molecular and biochemical basis for the dichotomy requires further investigation.
Supplementary Information: The online version contains supplementary material available at 10.1007/
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- doi:10.18112/
openneuro.ds003592.v1.0. — at OpenNeuro; found in the references13 - doi:10.18112/
openneuro.ds004215.v1.0. — at OpenNeuro; found in “Data availability”0[ - doi:10.18112/
openneuro.ds004215.v1.0. — at OpenNeuro; found in the references3 - doi:10.18112/
openneuro.ds004711.v1.0. — at OpenNeuro; found in the references0 - doi:10.18112/
openneuro.ds004746.v1.0. — at OpenNeuro; found in the references1 - openneuro:ds003592 — at OpenNeuro; found in “Data availability”
- openneuro:ds004711 — at OpenNeuro; found in “Data availability”
- openneuro:ds004746 — at OpenNeuro; found in “Data availability”
Data availability
The GM2 data described in this manuscript are available from the corresponding author upon reasonable request. Neurotypical control MRI data are available from OpenNeuro at the following links; NIMH :10.18112/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 3, 28 September 2026
- Publisher: — → Springer Science+Business Media
- Authors: added Katharine E Alter (0000-0002-5405-2143); Camilo Toro (0000-0002-3917-9031); Cynthia J Tifft (0000-0002-3931-1207); removed Katharine E Alter; Camilo Toro; Cynthia J Tifft
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 17 authors, 4 keywords, 14 MeSH terms, 7 funders, 81 references.
Cite
This paper
Lewis, C. J., Shirvan, L., Johnston, J. M., Groden, C., Yang, J., Ashton, A., Chong, J., Moran, M., Akmal, H., Chipman, S. I., Zampieri, C., Wickstrom, J., Matsubara, J., Lehky, T., Alter, K. E., Toro, C., & Tifft, C. J. (2026). Similarities and differences in the late-onset GM2 gangliosidoses: Tay-Sachs and Sandhoff diseases. Journal of neurology, 273(8), 504. https://
BibTeX
@article{lewis2026simila
author = {Lewis, Connor J and Shirvan, Leila and Johnston, Jean M and Groden, Catherine and Yang, John and Ashton, Andrea and Chong, Jessica and Moran, Mark and Akmal, Hera and Chipman, Selby I and Zampieri, Cris and Wickstrom, Jordan and Matsubara, Jesse and Lehky, Tanya and Alter, Katharine E and Toro, Camilo and Tifft, Cynthia J},
title = {{Similarities and differences in the late-onset GM2 gangliosidoses: Tay-Sachs and Sandhoff diseases}},
journal = {Journal of neurology},
year = {2026},
month = aug,
volume = {273},
number = {8},
pages = {504},
publisher = {Springer Science+Business Media},
issn = {0340-5354},
doi = {10.1007/
url = {https://
pmid = {42547667},
pmcid = {PMC13433390}
}
RIS
TY - JOUR
AU - Lewis, Connor J
AU - Shirvan, Leila
AU - Johnston, Jean M
AU - Groden, Catherine
AU - Yang, John
AU - Ashton, Andrea
AU - Chong, Jessica
AU - Moran, Mark
AU - Akmal, Hera
AU - Chipman, Selby I
AU - Zampieri, Cris
AU - Wickstrom, Jordan
AU - Matsubara, Jesse
AU - Lehky, Tanya
AU - Alter, Katharine E
AU - Toro, Camilo
AU - Tifft, Cynthia J
TI - Similarities and differences in the late-onset GM2 gangliosidoses: Tay-Sachs and Sandhoff diseases
T2 - Journal of neurology
J2 - J Neurol
PY - 2026
DA - 2026/
VL - 273
IS - 8
SP - 504
SN - 0340-5354
PB - Springer Science+Business Media
DO - 10.1007/
UR - https://
LA - en
ER -
CSL-JSON
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