ArticleJournal of inherited metabolic disease2020
Disturbed brain ether lipid metabolism and histology in Sjögren-Larsson syndrome.
Article in Journal of inherited metabolic disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Spatial lipidomics of the human brain: systematic review of current state and future perspectives.Molecular psychiatry · 2026Pooled it
- Article
- Clinical and genetic analysis of patients with Sjögren-Larsson syndrome in China.Orphanet journal of rare diseases · 2026Article
- Genotypic and Phenotypic Characteristics of Turkish Patients with Sjögren-Larsson Syndrome.Molecular syndromology · 2026Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Article
- Adipose transplantation improves olfactory function and neurogenesis via PKCα-involved lipid metabolism in Seipin Knockout mice.Stem cell research & therapy · 2023Article
- Sjogren-Larsson syndrome brain volumetric reductions demonstrated with an automated software.Arquivos de neuro-psiquiatria · 2023Article
- Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders.Molecular psychiatry · 2023Article
- Untargeted Metabolomic Analysis of Sjögren-Larsson Syndrome Reveals a Distinctive Pattern of Multiple Disrupted Biochemical Pathways.Metabolites · 2023Article
- Myelin lipid metabolism and its role in myelination and myelin maintenance.Innovation (Cambridge (Mass.)) · 2023Review
- Lipidomics-Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases.International journal of molecular sciences · 2023Review
- Ether lipids and a peroxisomal riddle in sperm.Frontiers in cell and developmental biology · 2023Review
- How to proceed after "negative" exome: A review on genetic diagnostics, limitations, challenges, and emerging new multiomics techniques.Journal of inherited metabolic disease · 2022Review
- ClinicalNeuroradiology · 2022Review
- Sjögren-Larsson syndrome: A biochemical rationale for using aldehyde-reactive therapeutic agents.Molecular genetics and metabolism reports · 2022Article
- Population Genomics ofBiology · 2022Article
- Tricky Isomers-The Evolution of Analytical Strategies to Characterize Plasmalogens and Plasmanyl Ether Lipids.Frontiers in cell and developmental biology · 2022Review
- Activation Mechanisms of the VPS34 Complexes.Cells · 2021Review
- ABHD16A deficiency causes a complicated form of hereditary spastic paraplegia associated with intellectual disability and cerebral anomalies.American journal of human genetics · 2021Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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