Vitamin D status and latitude predict brain lesions in adrenoleukodystrophy.

Approximately 40% of boys with X-linked adrenoleukodystrophy (ALD) develop inflammatory demyelinating brain lesions (cerebral ALD, cALD) and are at risk for death or severe disability. Risk factors for cALD are poorly understood. Our objective was to evaluate whether vitamin D status, which influences immune function, is associated with risk for cALD. We used two independent cohorts to assess whether low vitamin D status is correlated with cALD. We used complementary proxies for vitamin D status: plasma 25-hydroxyvitamin D levels and latitude. In our first cohort, we measured 25-hydroxyvitamin D in biobanked plasma samples from ALD boys with initially normal brain MRIs followed at two expert centers. In a second cohort, we measured latitude (using home ZIP code) among ALD boys identified in a national administrative database (PHIS) covering 51 US pediatric hospitals. We used logistic regression models to estimate the odds of developing cALD in each cohort. In the first cohort, we identified 20 ALD boys with a total of 53 plasma sample timepoints who met inclusion criteria; 50% ( Using independent cohorts, we found that ALD boys with lower pre-morbid plasma levels of 25-hydroxyvitamin D, or more northerly latitude of residence, were more likely to develop cALD. These findings offer complementary lines of evidence that vitamin D and/or ultraviolet light exposure influence cALD risk.

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© 2023 The Authors. Annals of the Child Neurology Society published by Wiley Periodicals LLC on behalf of the Child Neurology Society.

Déclaration de conflit d'intérêts

All authors have completed the ICMJE uniform disclosure form and declare that the study described in the submitted work was supported, in part, by the Child Neurology Foundation Scientific Award and NIH/NINDS K23NS087151; KV has received research grants from Bluebird bio and Minoryx for clinical trials in ALD participants, separate from the submitted work; consulting fees from bluebird bio, Minoryx, Viking Therapeutics, Poxel, and Orpheris for ALD therapy development separate from the submitted work. He participates in advisory boards for Poxel (paid), Viking (paid), ALD Connect (unpaid), and the United Leukodystrophy Foundation (unpaid). GVR has received consulting fees from bluebird bio, from Viking Therapeutics, and for therapy development outside the submitted work. JLB has received research support from Sanofi and Autobahn as well as consulting fees from Neurogene, Passage Bio, Takeda, and Autobahn all for work outside the submitted work. He is an unpaid board member at ALD Connect and wFluidx. No other relationships or activities that could appear to have influenced the submitted work.