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Disturbed brain ether lipid metabolism and histology in Sjögren-Larsson syndrome
- Source :
- Journal of Inherited Metabolic Disease, Staps, P, Rizzo, W B, Vaz, F M, Bugiani, M, Giera, M, Heijs, B, van Kampen, A H C, Pras-Raves, M L, Breur, M, Groen, A, Ferdinandusse, S, van der Graaf, M, Van Goethem, G, Lammens, M, Wevers, R A & Willemsen, M A A P 2020, ' Disturbed brain ether lipid metabolism and histology in Sjögren-Larsson syndrome ', Journal of Inherited Metabolic Disease, vol. 43, no. 6, pp. 1265-1278 . https://doi.org/10.1002/jimd.12275, Journal of inherited metabolic disease, Journal of Inherited Metabolic Disease, 43(6), 1265-1278. Springer Netherlands, Journal of Inherited Metabolic Disease, 43(6), 1265-1278. WILEY, Journal of Inherited Metabolic Disease, 43, 6, pp. 1265-1278, Journal of Inherited Metabolic Disease, 43, 1265-1278, Journal of inherited metabolic disease, 43(6), 1265-1278. Springer Netherlands
- Publication Year :
- 2020
-
Abstract
- Contains fulltext : 229584.pdf (Publisher’s version ) (Open Access) Sjögren-Larsson syndrome (SLS) is a rare neurometabolic syndrome caused by deficient fatty aldehyde dehydrogenase. Patients exhibit intellectual disability, spastic paraplegia, and ichthyosis. The accumulation of fatty alcohols and fatty aldehydes has been demonstrated in plasma and skin but never in brain. Brain magnetic resonance imaging and spectroscopy studies, however, have shown an abundant lipid peak in the white matter of patients with SLS, suggesting lipid accumulation in the brain as well. Using histopathology, mass spectrometry imaging, and lipidomics, we studied the morphology and the lipidome of a postmortem brain of a 65-year-old female patient with genetically confirmed SLS and compared the results with a matched control brain. Histopathological analyses revealed structural white matter abnormalities with the presence of small lipid droplets, deficient myelin, and astrogliosis. Biochemically, severely disturbed lipid profiles were found in both white and gray matter of the SLS brain, with accumulation of fatty alcohols and ether lipids. Particularly, long-chain unsaturated ether lipid species accumulated, most prominently in white matter. Also, there was a striking accumulation of odd-chain fatty alcohols and odd-chain ether(phospho)lipids. Our results suggest that the central nervous system involvement in SLS is caused by the accumulation of fatty alcohols leading to a disbalance between ether lipid and glycero(phospho)lipid metabolism resulting in a profoundly disrupted brain lipidome. Our data show that SLS is not a pure leukoencephalopathy, but also a gray matter disease. Additionally, the histopathological abnormalities suggest that astrocytes and microglia might play a pivotal role in the underlying disease mechanism, possibly contributing to the impairment of myelin maintenance.
- Subjects :
- Sjögren-Larsson syndrome
medicine.medical_specialty
brain
Vascular damage Radboud Institute for Health Sciences [Radboudumc 16]
mass spectrometry imaging
White matter
03 medical and health sciences
chemistry.chemical_compound
Internal medicine
Lipid droplet
Lipidomics
Genetics
medicine
Humans
ether lipids
Genetics (clinical)
phospholipids
030304 developmental biology
Aged
Sjögren‐Larsson syndrome
0303 health sciences
Sjögren–Larsson syndrome
030305 genetics & heredity
Lipid metabolism
odd-chain fatty alcohols
Original Articles
Lipidome
fatty aldehyde dehydrogenase
medicine.disease
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
Lipid Metabolism
Magnetic Resonance Imaging
odd‐chain fatty alcohols
Sjogren-Larsson Syndrome
Ether lipid
Endocrinology
medicine.anatomical_structure
chemistry
Myelin maintenance
lipidomics
Female
Original Article
pathology
Human medicine
Fatty Alcohols
Ethers
Subjects
Details
- Language :
- English
- ISSN :
- 01418955
- Volume :
- 43
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of Inherited Metabolic Disease
- Accession number :
- edsair.doi.dedup.....781e1d007f55fc9568293faf0b68d494