Abstract Details

Title Vitamin D Status as a Risk Factor for Cerebral Demyelination in X-Linked Adrenoleukdystrophy

Topic MS and Related Diseases

Presentation(s) S60 - (-)

Poster/Presentation
Number 005

Objective

Background ALD is a monogenetic peroxisomal disorder (ABCD1 gene; 1:17,000) characterized by elevated levels of very long chain fatty acids. Approximately 40% of ALD boys develop inflammatory cerebral demyelination between 4 and 12 years of age. The risk factors associated with cerebral demyelination are unknown.

Design/Methods Plasma samples were collected prospectively and biobanked at -80C as part of a single center longitudinal cohort. Patients were selected for this study based on the availability of plasma from at least two timepoints prior to clinical endpoint. The clinical endpoints were defined as 1) the diagnosis of cerebral demyelination or 2) the end of clinical follow-up with no demyelination. ALD boys who developed cerebral demyelination (n=8) were age-matched with ALD boys (n=8) who had no cerebral demyelination. 25-OH vitamin D levels were measured via LCMSMS by a blinded third party (Heartland Assays, Inc). We used a previously described algorithm to adjust 25-OH levels for date of blood draw. We used Mann-Whitney test (Prism software)to directly compare the average deseasonalized 25-OH levels between the two groups. We used a generalized estimating equation (STATA software) to estimate the odds ratio of developing cerebral demyelination based on the unadjusted 25-OH level.

Results We found that the average deseasonalized 25-OH level was significantly lower in the ALD boys who later developed cerebral demyelination (p=0.05). We also found that each 10ng/ml increase in unadjusted vitamin D is associated with an odds ratio of cerebral demyelination of 0.26 (95%CI 0.05,1.35), p=0.109.

Conclusions Low plasma vitamin D levels may be a risk factor for cerebral demyelination in ALD boys. If confirmed, these findings would provide a rationale for a clinical trial of vitamin D to prevent cerebral demyelination in ALD boys.

Authors/Disclosures
Keith Van Haren, MD (Stanford Univ Neurology) PRESENTER	Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viking Therapeutics. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bluebirdbio. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Orpheris. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Autobahn. Dr. Van Haren has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for PRIME, Inc. The institution of Dr. Van Haren has received research support from Minoryx. The institution of Dr. Van Haren has received research support from bluebirdbio. Dr. Van Haren has a non-compensated relationship as a Board of Directors with ALD Connect that is relevant to AAN interests or activities. Dr. Van Haren has a non-compensated relationship as a Scientific Advisory Board with United Leukodystrophy Foundation that is relevant to AAN interests or activities.
Ellen M. Mowry, MD, FAAN (Johns Hopkins University)	Dr. Mowry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BeCareLink, LLC. The institution of Dr. Mowry has received research support from Biogen. The institution of Dr. Mowry has received research support from Genentech. Dr. Mowry has received publishing royalties from a publication relating to health care.
Gerald Raymond, MD (Johns Hopkins)	Dr. Raymond has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Bluebird bio. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Ionis. Dr. Raymond has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Travere. Dr. Raymond has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant with Dept of HHS.
	No disclosure on file
Lawrence Steinman, MD, FAAN (Stanford Medicine)	Dr. Steinman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for 180 Life Sciences. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for BioAtla. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Pasithea. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Atreca. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Wilmer Hale Cutler Pickering. Dr. Steinman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Meyers Squibb. Dr. Steinman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Steinman has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for National Academy of Sciences. Dr. Steinman has received personal compensation in the range of $100,000-$499,999 for serving as an Expert Witness for Gibson Dunn. The institution of Dr. Steinman has received research support from Roche. The institution of Dr. Steinman has received research support from Novartis. Dr. Steinman has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file

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