Abstract
AbstractX-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
Funder
Austrian Science Fund
Association Européenne contre les Leucodystrophies
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Reference39 articles.
1. Moser, A. B. et al. Newborn screening for X-linked adrenoleukodystrophy. Int. J. Neonatal Screen. 2, 15 (2016).
2. Moser H. W. S. K. D., Watkins P. A., Powers J., Moser A. B. in The Online Metabolic & Molecular Bases of Inherited Disease (eds. Valle D. Vogelstein B. K. K. W., Antonarakis S. E., Ballabio A., Gibson M., Mitchell G. B. A. L.) 3257–3301 (2007).
3. Mosser, J. et al. Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 361, 726–730 (1993).
4. Wiesinger, C., Kunze, M., Regelsberger, G., Forss-Petter, S. & Berger, J. Impaired very long-chain acyl-CoA beta-oxidation in human X-linked adrenoleukodystrophy fibroblasts is a direct consequence of ABCD1 transporter dysfunction. J. Biol. Chem. 288, 19269–19279 (2013).
5. Berger, J. & Gartner, J. X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects. Biochim. Biophys. Acta 1763, 1721–1732 (2006).
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