Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (678 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An X-linked recessive disorder characterized by the accumulation of saturated very long chain fatty acids in the lysosomes of adrenal cortex and the white matter of central nervous system. This disease occurs almost exclusively in the males. Clinical features include the childhood onset of ataxia; neurobehavioral manifestations; hyperpigmentation; adrenal insufficiency; seizures; muscle spasticity; and dementia. The slowly progressive adult form is called adrenomyeloneuropathy. The defective gene abcd1 is located at Xq28, and encodes the adrenoleukodystrophy protein (atp-binding cassette transporters).
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Bronze Schilder Disease; Melanodermic Leukodystrophy; Leukodystrophies, Melanodermic; Leukodystrophy, Melanodermic; Siemerling-Creutzfeldt Disease; Siemerling Creutzfeldt Disease; Schilder-Addison Complex; Schilder Addison Complex.
Where it fits in the MeSH classification
- Broader topics
- Brain Diseases, Metabolic, Inborn; Hereditary Central Nervous System Demyelinating Diseases; X-Linked Intellectual Disability; Peroxisomal Disorders; Adrenal Insufficiency
- See also
- ATP-Binding Cassette Transporters
Related concepts
- Lysosomes
- Adrenal Cortex
- Central Nervous System
- Ataxia
- Neurobehavioral Manifestations
- Hyperpigmentation
- Adrenal Insufficiency
- Seizures
- Muscle Spasticity
- Dementia
Research landscape
PubMed indexes 2,048 records tagged with the MeSH heading “Adrenoleukodystrophy” (counts retrieved 2026-10-29). 319 of them (15.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 820 records.
Reviews account for 294 records (14.4%) and meta-analyses for 2. Randomized controlled trials number 8 (0.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 820 |
| 2000-2009 | 460 |
| 2010-2019 | 449 |
| 2020 onward | 319 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 294 | 14.4% |
| Meta-analyses | 2 | 0.1% |
| Randomized controlled trials | 8 | 0.4% |
Method: PubMed query "Adrenoleukodystrophy"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management [1]
Abstract reading summary — source excerpts
- Opening excerpt
- X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder.
- Closing excerpt
- This review focuses on the diagnosis and management of patients with X-ALD and provides a guideline for clinicians that encounter patients with this highly complex disorder.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (123 words)
X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is caused by mutations in the ABCD1 gene that encodes the peroxisomal membrane protein ALDP which is involved in the transmembrane transport of very long-chain fatty acids (VLCFA; ≥ C22). A defect in ALDP results in elevated levels of VLCFA in plasma and tissues. The clinical spectrum in males with X-ALD ranges from isolated adrenocortical insufficiency and slowly progressive myelopathy to devastating cerebral demyelination. The majority of heterozygous females will develop symptoms by the age of 60 years. In individual patients the disease course remains unpredictable. This review focuses on the diagnosis and management of patients with X-ALD and provides a guideline for clinicians that encounter patients with this highly complex disorder.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 22889154 · DOI · PMC3503704
X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Adrenoleukodystrophy (ALD) is a rare X-linked disease caused by a mutation of the peroxisomal ABCD1 gene.
- Closing excerpt
- The continuing increase in newborn screening programs and promising results from ongoing and recent therapeutic investigations provide hope for ALD.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (115 words)
Adrenoleukodystrophy (ALD) is a rare X-linked disease caused by a mutation of the peroxisomal ABCD1 gene. This review summarizes our current understanding of the pathogenic cell- and tissue-specific roles of lipid species in the context of experimental therapeutic strategies and provides an overview of critical historical developments, therapeutic trials and the advent of newborn screening in the USA. In ALD, very long-chain fatty acid (VLCFA) chain length-dependent dysregulation of endoplasmic reticulum stress and mitochondrial radical generating systems inducing cell death pathways has been shown, providing the rationale for therapeutic moiety-specific VLCFA reduction and antioxidant strategies. The continuing increase in newborn screening programs and promising results from ongoing and recent therapeutic investigations provide hope for ALD.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 31909500 · DOI · PMC7041623
International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Pathogenic variants in the ABCD1 gene cause adrenoleukodystrophy (ALD), a progressive metabolic disorder characterized by 3 core clinical syndromes: a slowly progressive myeloneuropathy, a rapidly progressive inflammatory leukodystrophy (cerebral ALD), and primary adrenal insufficiency.
- Closing excerpt
- This knowledge gap should direct future research and illustrates once again that international collaboration among physicians, researchers, and patients is essential to improving care.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (228 words)
Pathogenic variants in the ABCD1 gene cause adrenoleukodystrophy (ALD), a progressive metabolic disorder characterized by 3 core clinical syndromes: a slowly progressive myeloneuropathy, a rapidly progressive inflammatory leukodystrophy (cerebral ALD), and primary adrenal insufficiency. These syndromes are not present in all individuals and are not related to genotype. Cerebral ALD and adrenal insufficiency require early detection and intervention and warrant clinical surveillance because of variable penetrance and age at onset. Newborn screening has increased the number of presymptomatic individuals under observation, but clinical surveillance protocols vary. We used a consensus-based modified Delphi approach among 28 international ALD experts to develop best-practice recommendations for diagnosis, clinical surveillance, and treatment of patients with ALD. We identified 39 discrete areas of consensus. Regular monitoring to detect the onset of adrenal failure and conversion to cerebral ALD is recommended in all male patients. Hematopoietic cell transplant (HCT) is the treatment of choice for cerebral ALD. This guideline addresses a clinical need in the ALD community worldwide as the number of overall diagnoses and presymptomatic individuals is increasing because of newborn screening and greater availability of next-generation sequencing. The poor ability to predict the disease course informs current monitoring intervals but remains subject to change as more data emerge. This knowledge gap should direct future research and illustrates once again that international collaboration among physicians, researchers, and patients is essential to improving care.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36175155 · DOI · PMC9687408
Phosphatidylcholine with C26:0 moiety, a precursor of a diagnostic marker for X-ALD, is synthesized by LPLAT10/LPEAT2 [4]
Abstract reading summary — source excerpts
- Opening excerpt
- X-linked adrenoleukodystrophy (X-ALD) is a congenital metabolic disorder characterized mainly by inflammatory demyelination and adrenal insufficiency.
- Closing excerpt
- These results suggest that C26:0-LPC is produced through acyl-chain remodeling of PC catalyzed by LPLAT10 and accumulates in the plasma from X-ALD patients.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (212 words)
X-linked adrenoleukodystrophy (X-ALD) is a congenital metabolic disorder characterized mainly by inflammatory demyelination and adrenal insufficiency. Newborn screening using hexacosanoyl lysophosphatidylcholine (C26:0-LPC) in dried blood spots as a diagnostic marker can successfully identify potential patients with X-ALD and prevent disease onset. C26:0-LPC accumulates in patients with X-ALD, although the machinery synthesizing it has remained unclear. In this study, we focused on phosphatidylcholine (PC) with C26:0 moiety as a precursor of C26:0-LPC. We identified that lysophospholipid (LPL) acyltransferase 10 (LPLAT10)/LPCAT4/LPEAT2/AGPAT7 (1-acylglycerol-3-phosphate O-acyltransferase 7) is the responsible LPL acyltransferase that produces PC with C26:0 moiety by transferring C26:0-CoA into 2-acyl-LPC. We also found that LPLAT10 deficiency decreased the amount of C26:0-LPC in fibroblasts from X-ALD patients. Mechanistically, LPLAT10 introduced saturated fatty acid-CoA of various chain lengths as substrates into the sn-1 position of LPC but did not transfer C26:0-CoA to other LPL classes, such as lysophosphatidylethanolamine. Structural analysis revealed that a trimethylamine group of PC was placed between two tryptophan residues (W242 and W244), forming a W-X-W motif, possibly through cation-π interaction. Finally, it was shown that exogenously administered C26:0 FFA-d4 was preferentially incorporated into sphingolipids in the absence of LPLAT10. These results suggest that C26:0-LPC is produced through acyl-chain remodeling of PC catalyzed by LPLAT10 and accumulates in the plasma from X-ALD patients.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41478358 · DOI · PMC12859765
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy [5]
- Research article X-linked adrenoleukodystrophy [6]
- Research article ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations [7]
- Research article X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects [8]
- Research article Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history [9]
- Research article Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation [10]
References
- Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, et al.. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. . 2012. PMID 22889154 · DOI · PMC3503704
- Turk BR, Theda C, Fatemi A, Moser AB. X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies. . 2020. PMID 31909500 · DOI · PMC7041623
- Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, et al.. International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach. . 2022. PMID 36175155 · DOI · PMC9687408
- Hama K, Fujiwara Y, Imai K, Kusakabe Y, Hayashi Y, Takashima S, et al.. Phosphatidylcholine with C26:0 moiety, a precursor of a diagnostic marker for X-ALD, is synthesized by LPLAT10/LPEAT2. . 2026. PMID 41478358 · DOI · PMC12859765
- Moser HW. Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain. 1997. PMID 9278636 · DOI
- Moser HW, Mahmood A, Raymond GV. X-linked adrenoleukodystrophy. Nat Clin Pract Neurol. 2007. PMID 17342190 · DOI
- Kemp S, Pujol A, Waterham HR, van Geel BM, Boehm CD, Raymond GV, et al.. ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Hum Mutat. 2001. PMID 11748843 · DOI
- Kemp S, Berger J, Aubourg P. X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta. 2012. PMID 22483867 · DOI
- Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M. Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol. 2016. PMID 27312864 · DOI
- Shapiro EG, Lockman LA, Balthazor M, Krivit W. Neuropsychological outcomes of several storage diseases with and without bone marrow transplantation. J Inherit Metab Dis. 1995. PMID 7494400 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.