Fatty acid abnormality in adrenoleukodystrophy
Abstract
—Recent clinical and morphological evidence established that adrenoleukodystrophy is a distinct X‐linked genetic disorder. Fatty acid compositions of lipids in the brain, adrenal and serum from seven patients were examined. Cholesterol esters of both brain and adrenal contained substantial proportions of fatty acids longer than C 22 (11.8–41.9% of total in the brain and 13.4‐34.8% of total in the adrenal), while cholesterol esters from normal and pathological control specimens contained very little. These very long chain fatty acids were generally saturated in brain cholesterol esters but significant amounts of unsaturated long chain fatty acids were also present in adrenal cholesterol esters. The long chain fatty acids showed bell‐shaped distribution with C 25 or C 26 at the peak. Ganglio‐sides from patients’white matter also showed increased proportions of very long‐chain fatty acids, up to 50% of the total. Qualitatively similar but much milder fatty acid abnormalities were also found in galactosylceramide of the brain. On the other hand, fatty acids and fatty aldehydes of brain glycerophospholipids, adrenal free fatty acids, triglycerides and glycerophospholipids were not abnormal. Furthermore, serum cholesterol esters from two patients did not show the long‐chain fatty acid abnormality found in brain and adrenal cholesterol esters. Sequential extractions with acetone and hexane established that the characteristic birefringent material in the brain and adrenal is indeed cholesterol esters with very long chain fatty acids. This type of fatty acid abnormality has not been described in other pathological conditions and may well represent the unique biochemical abnormality that is directly related to the fundamental genetic defect underlying adrenoleukodystrophy.
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In 1976, accumulation of very-long-chain fatty acids was discovered in brain white matter of X-ALD.
“In 1976, the discovery of the accumulation of very-long-chain fatty acids (VLCFAs) in brain white matter [22] opened up a biochemical avenue to X-ALD pathophysiology.”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [22]
Electron microscopy reveals characteristic cytoplasmic inclusions (spicules) in oligodendrocytes, perivascular macrophages, and/or microglia but not in astrocytes.
“Electron microscopy reveals characteristic cytoplasmic inclusions (“spicules”) in OLs, perivascular macrophages, and/or microglia but not in astrocytes.”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [22]
Cytoplasmic inclusions (spicules) made of cholesterol, phospholipids, and gangliosides esterified with saturated VLCFAs were found in human brain oligodendrocytes and macrophages and in adrenal cells or Schwann cells.
“Cytoplasmic inclusions (“spicules”) made of cholesterol, phospholipids, and gangliosides esterified with saturated VLCFAs [22] were found in human brain OL and macrophages and in adrenal cells or Schwann cells [167].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [22]
VLCFAs in plasma are a diagnostic marker for ALD.
“VLCFAs in plasma are a diagnostic marker.5,6”
From International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy (2022) · cites this paper as [6]
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“4,5 Despite numerous studies, pathophysiology remains incompletely understood.”
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- Authors
- Igarashi, M., Schaumburg, H. H., Powers, J., Kishimoto, Y., Koilodny, E., & Suzuki, K.
- Affiliations
- Albert Einstein College of Medicine (US)
- Corresponding author
- Suzuki, K.
- ORCID
- Powers, J.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1976-04
- Volume
- 26
- Issue
- 4
- Pages
- 851-860
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W4232666095
- Cited by
- 134
- References
- 33
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 12 · 2023: 1 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 4 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- adrenoleukodystrophy, very long chain fatty acids, cholesterol esters, fatty acid composition, brain lipids, gangliosides, galactosylceramide, X-linked disorders, white matter pathology, birefringent materials
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