Vitamin D Status as a Risk Factor for Cerebral Demyelination in X-Linked Adrenoleukdystrophy (S60.005)

Abstract

OBJECTIVE: To determine whether low vitamin levels are associated with an increased risk of cerebral demyelination in boys with X-linked adrenoleukodystrophy (ALD).

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.

Supported by: Scientific Award from the Child Neurology Foundation; Sprague-McHugh Family Award from the Lucile Packard Foundation; NIH Loan Repayment Program.

Disclosure: Dr. Van Haren has nothing to disclose. Dr. Mowry has received research support from Teva Neuroscience. Dr. Raymond has received personal compensation for activities with from Bluebird Bio as a speaker. Dr. Raymond has received research support from Bluebird Bio. Dr. Moser has nothing to disclose. Dr. Steinman has received personal compensation for activies with Biogen-Idec, Teva, MedImmune, Sanofi, and Bayer.