Abstract Details

Title Imaging in Late-Onset GM2 Gangliosidosis: A Systematic Review

Topic Movement Disorders

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 280

Objective We systematically analyzed published data in late-onset GM2 gangliosidosis, (LOGG) subtypes late-onset Tay Sachs disease (LOTS) and Sandhoff disease (LOSD) to ascertain whether specific brain imaging and clinical features may differentiate these LOGG subtypes.

Background

LOTS and LOSD are ultra-rare neurodegenerative lysosomal storage disorders involving a combination of weakness, ataxia and neuropsychiatric symptoms. Previous studies have considered LOTS and LOSD to be clinically indistinguishable, while recent studies have challenged this notion.

Design/Methods We examined MEDLINE and non-MEDLINE databases up to July 2021. English articles reporting brain imaging findings in genetically/enzymatically-confirmed LOGG and symptom onset after age 10 (or evaluated at least once at age 18 or older) were included. This yielded 161 individual LOGG patients (LOTS=120, LOSD=41) across 65 papers.

Results The mean age of symptom onset was lower in LOTS vs. LOSD (p=0.017) and younger-onset (age <18) LOGG patients were more likely to have psychiatric symptoms (p=0.0087). Cerebellar atrophy was more common in LOTS (88.3%) vs. LOSD (63.4%), (p=0.0003) and LOTS had a higher severity of atrophy (p=0.0003). Brainstem atrophy was only documented in LOTS (10.8%).Cerebellar atrophy was more common in younger-onset LOGG (89.2%) vs. age 18+ (76.1%), p=0.039, even when controlling for disease duration. LOTS patients had similar rates of cerebellar atrophy in those with (89.7%) and without ataxia (82.8%), p=0.33, while in LOSD cerebellar atrophy was more common in ataxic (76.9%) vs. non-ataxic patients (40.0%), p=0.018. On logistic regression analysis, diagnosis of LOTS (p=0.0020) and reported ataxia (p=0.021) were independent predictors of cerebellar atrophy.

Conclusions This systematic review suggests that there are significant differences in symptomatology, disease course, and imaging findings between LOTS and LOSD. Further improving imaging characterization may help differentiate these LOGG subtypes at an earlier disease stage. These data suggest that LOTS and LOSD should be analyzed separately in future clinical trials.

Authors/Disclosures
Elizabeth Haxton, MD (Rhode Island Hospital) PRESENTER	Dr. Haxton has nothing to disclose.
Neha Godbole	Ms. Godbole has nothing to disclose.
Olivia Rowe	No disclosure on file
Florian Eichler, MD (Massachusetts General Hospital)	An immediate family member of Dr. Eichler has received personal compensation for serving as an employee of UpToDate. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Atlas Venture. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Acadia Pharmaceuticals. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Leal Therapeutics. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orchard Tx. Dr. Eichler has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis Therapeutics. The institution of Dr. Eichler has received research support from ASPA Therapeutics. The institution of Dr. Eichler has received research support from Abbvie. The institution of Dr. Eichler has received research support from Ionis Pharmaceuticals.
	No disclosure on file
Christopher D. Stephen, MB ChB, FRCP, MSc, SM	The institution of Dr. Stephen has received research support from Sanofi. Dr. Stephen has received research support from National Institutes of Health.

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