Vitamin D status and latitude predict brain lesions in adrenoleukodystrophy.

Autor: van Haren KP; Division of Child Neurology, Department of Neurology Stanford University California Palo Alto USA., Wilkes J; Intermountain Healthcare Utah Salt Lake City USA., Moser AB; Peroxisomal Disease Laboratory Kennedy Krieger Institute Maryland Baltimore USA., Raymond GV; Department of Neurology Johns Hopkins University School of Medicine Maryland Baltimore USA.; Department of Genetic Medicine Johns Hopkins University School of Medicine Maryland Baltimore USA., Richardson T; Research and Statistics Children's Hospital Association Kansas Lenexa USA., Aubourg P; INSERM U 1169 Paris-Sud University Le Kremlin-Bicêtre France.; Department of Pediatric Neurology, APHP Bicêtre University Hospital Le Kremlin-Bicêtre France., Collins TW; Department of Geography University of Utah Utah Salt Lake City USA., Mowry EM; Department of Neurology Johns Hopkins University School of Medicine Maryland Baltimore USA., Bonkowsky JL; Division of Pediatric Neurology, Department of Pediatrics University of Utah School of Medicine Utah Salt Lake City USA.; Brain and Spine Center Primary Children's Hospital Utah Salt Lake City USA.; Primary Children's Center for Personalized Medicine Utah Salt Lake City USA.
Jazyk: angličtina
Zdroj: Annals of the Child Neurology Society [Ann Child Neurol Soc] 2023 Jun; Vol. 1 (2), pp. 155-161. Date of Electronic Publication: 2023 Apr 18.
DOI: 10.1002/cns3.4
Abstrakt: Objectives: 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.
Methods: 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.
Results: In the first cohort, we identified 20 ALD boys with a total of 53 plasma sample timepoints who met inclusion criteria; 50% ( n = 10) subsequently developed cALD. Average 25-hydroxyvitamin D levels were lower among boys who developed cALD than those who did not (median 28.9 vs 36.6 ng/ml); p = 0.019. For each 10 ng/mL decrease in 25-hydroxyvitamin D, the odds ratio for developing cALD was 6.94; p = 0.044. In the second cohort, we identified 230 ALD boys across 28 states; 57% of boys ( n = 132) developed cALD. Each 2° increase in latitude conferred an odds ratio of 1.17 (95% confidence interval, 1.01, 1.35); p = 0.036 for developing cALD.
Conclusions: 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.
Competing Interests: 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.
(© 2023 The Authors. Annals of the Child Neurology Society published by Wiley Periodicals LLC on behalf of the Child Neurology Society.)
Databáze: MEDLINE
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