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Cited by 131Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchNeurological diseases and metabolism

Progression of abnormalities in adrenomyeloneuropathy and neurologically asymptomatic X-linked adrenoleukodystrophy despite treatment with "Lorenzo's oil"

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van Geel, B M, Assies, J, Haverkort, E B, Koelman, J H T M, Verbeeten, B, Wanders, R J A, Barth, P G·1999·Journal of Neurology, Neurosurgery & Psychiatry
DOI 10.1136/jnnp.67.3.290PMC PMC1736534
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Abstract

OBJECTIVES: X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder of peroxisomal fatty acid oxidation, biochemically characterised by the accumulation of saturated very long chain fatty acids (VLCFAs), particularly hexacosanoic acid (C26:0). Dietary treatment with a 4:1 mixture of glyceroltrioleate and glyceroltrierucate ("Lorenzo's oil") normalises plasma VLCFA concentrations, but neither ameliorates nor arrests the rapid progression of neurological symptoms in the cerebral variants of X-ALD. The efficacy of "Lorenzo's oil" in the milder phenotypes of X-ALD was assessed, as this has been much less investigated. METHODS: Twenty two patients who were treated with "Lorenzo's oil" for at least 12 months for a median period of 2.5 (range 1.0-6.0) years were studied. Two had asymptomatic ALD, four the "Addison only" variant, 13 adrenomyeloneuropathy (AMN), and three were symptomatic female carriers. RESULTS: The plasma C26:0 concentration normalised or near normalised in 19 patients (86%), in the three others it decreased significantly. Nevertheless, disability as measured with the extended disability status scale score increased mildly (0.5 (95% confidence interval (95% CI) 0.25-1.0)) in the 16 patients with neurological symptoms. Furthermore, one "Addison only" patient and one patient with AMN developed cerebral demyelination, and another "Addison only" patient developed AMN. Adrenocortical insufficiency evolved in one patient with AMN, and hypogonadism in one patient with asymptomatic ALD and two patients with AMN. Nerve conduction, evoked potential studies (SEP, BAEP, VEP), and abnormalities on cerebral MRI did not improve. On the other hand, side effects were often noted-namely, mild increases in liver enzymes (55%), thrombocytopenia (55%), gastrointestinal complaints (14%), and gingivitis (14%). We also found a mild decrease in haemoglobin concentration and leucocyte count. CONCLUSIONS: The data suggest that treatment with "Lorenzo's oil" neither improved neurological or endocrine function nor arrested progression of the disease. Furthermore, the oil often induced adverse effects. Therefore, it is advocated that "Lorenzo's oil" should not be prescribed routinely to patients with X-ALD who already have neurological deficits.

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  • Peripheral neuropathy is a common feature of ALD but is rarely the presenting symptom.

    “Peripheral neuropathy is a common feature of ALD but is rarely the presenting symptom.7,14-16”

    From International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy (2022) · cites this paper as [16]

    The ELECTRONEUROGRAPHY section (page not specified) reports nerve-conduction abnormalities in 12 of 16 neurologically symptomatic patients, most often compatible with sensorimotor polyneuropathy. This supports peripheral neuropathy as a common feature in the studied symptomatic patients, but the paper does not establish that it is rarely the presenting symptom. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Dietary therapy with 'Lorenzo's Oil' does not appear to alter the course of neurologic progression in patients who already have neurologic symptoms.

    “but does not appear to alter the course of neurologic progression in patients who already have neurologic symptoms [van Geel et al., 1999]”

    From ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations (2001) · cites this paper as van Geel et al., 1999

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Cited by

Sorted by citations

Authors
van Geel, B. M., Assies, J., Haverkort, E. B., Koelman, J. H. T. M., Verbeeten, B., Wanders, R. J. A., & Barth, P. G.
Affiliations
Amsterdam UMC Location University of Amsterdam (NL)
ORCID
Venue
Journal of Neurology, Neurosurgery & Psychiatry
Publisher
BMJ
Published
1999-09-01
Volume
67
Issue
3
Pages
290-299
ISSN
0022-3050 (ISSN-L)
DOI
10.1136/jnnp.67.3.290
PMC
PMC1736534
OpenAlex
W2008239986
Cited by
131
References
8
Citations by year
2026: 2 · 2025: 2 · 2024: 7 · 2023: 1 · 2022: 9 · 2021: 3 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 7 · 2013: 7 · 2012: 3
FWCI
3.35
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UvA-DARE (University of Amsterdam) (publishedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion)
Funders
Universiteit van Amsterdam
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
X-linked adrenoleukodystrophy, adrenomyeloneuropathy, Lorenzo's oil, very long chain fatty acids, hexacosanoic acid, peroxisomal fatty acid oxidation, disease progression, neurological deficit, adrenal insufficiency, hypogonadism, brain demyelination, treatment side effects
MeSH terms
Adolescent, Adrenoleukodystrophy, Adult, Brain, Child, Child, Preschool, Dietary Fats, Unsaturated, Drug Combinations, Endocrine System, Erucic Acids, Evoked Potentials, Female, Humans, Genetic Linkage, Magnetic Resonance Imaging, Male, Triolein, X Chromosome

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