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 (713 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
A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; tendons; joints of knees and elbows. Xanthomatosis is associated with disturbance of lipid metabolism and formation of foam cells.
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: Xanthomatoses; Xanthoma; Xanthomas.
Where it fits in the MeSH classification
- Broader topics
- Lipid Metabolism Disorders
- Narrower topics
- Necrobiotic Xanthogranuloma; Xanthomatosis, Cerebrotendinous
Related concepts
- Tendons
- Knees
- Elbows
- Lipid Metabolism
- Foam Cells
Research landscape
PubMed indexes 5,714 records tagged with the MeSH heading “Xanthomatosis” (counts retrieved 2026-10-31). 571 of them (10.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 3,201 records.
Reviews account for 497 records (8.7%) and meta-analyses for 4. Randomized controlled trials number 12 (0.2%) 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 | 3,201 |
| 2000-2009 | 792 |
| 2010-2019 | 1,150 |
| 2020 onward | 571 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 497 | 8.7% |
| Meta-analyses | 4 | 0.1% |
| Randomized controlled trials | 12 | 0.2% |
Method: PubMed query "Xanthomatosis"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in metabolism and endocrine disease
Studies of diabetes, obesity and hormone disorders often follow blood tests such as glucose, HbA1c or hormone levels, which are stand-ins for outcomes that matter more, such as complications. Lifestyle and diet research is largely observational, and weight and diabetes trials can differ in how long people were followed. Nothing on this page is advice about medicines, insulin or diet; talk to a qualified clinician about your own situation. Check whether the outcome was a lab value or a clinical event, and the type and duration of the condition studied.
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.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Natural history of cerebrotendinous xanthomatosis: a paediatric disease diagnosed in adulthood | 2016 | Research article Design not recorded in structured metadata | 50 | cc by PMID 27084087 · DOI · PMC4833925 |
| Systemic therapy of necrobiotic xanthogranuloma: a systematic review | 2022 | Systematic review Design not recorded in structured metadata | 25 | cc by PMID 35331271 · DOI · PMC8944121 |
| Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis | 2023 | Research article Design not recorded in structured metadata | 22 | cc by PMID 36650582 · DOI · PMC9843874 |
| Cerebrotendinous xanthomatosis: A complex interplay between a clinically and genetically heterogeneous condition | 2025 | Research article Design not recorded in structured metadata | 4 | cc by PMID 39760285 · DOI · PMC11702487 |
Natural history of cerebrotendinous xanthomatosis: a paediatric disease diagnosed in adulthood [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Cerebrotendinous xanthomatosis (CTX) is among the few inherited neurometabolic disorders amenable to specific treatment.
- Closing excerpt
- It appears critical to raise awareness about CTX among paediatricians in order to initiate treatment before irreversible damage occurs.
- 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 (102 words)
Cerebrotendinous xanthomatosis (CTX) is among the few inherited neurometabolic disorders amenable to specific treatment. It is easily diagnosed using plasma cholestanol. We wished to delineate the natural history of the most common neurological and non-neurological symptoms in thirteen patients with CTX. Diarrhea almost always developed within the first year of life. Cataract and school difficulties usually occurred between 5 and 15 years of age preceding by years the onset of motor or psychiatric symptoms. The median age at diagnosis was 24.5 years old. It appears critical to raise awareness about CTX among paediatricians in order to initiate treatment before irreversible damage occurs.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 27084087 · DOI · PMC4833925
Systemic therapy of necrobiotic xanthogranuloma: a systematic review [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundEven though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature.
- Closing excerpt
- ConclusionsCorticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.
- 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 (111 words)
BackgroundEven though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature.ObjectiveTo review all existing literature on the systemic therapy of NXG in order to identify the most effective therapies.MethodsAll reported papers in the literature were screened for systemic treatments of NXG. Papers without proper description of the therapies, papers describing topical therapy, and articles without assessment of effectiveness were excluded. Subsequently, we analyzed 79 papers and a total of 175 cases.ResultsThe most effective treatments for NXG are intravenous immunoglobulins (IVIG), corticosteroids, and combination therapies including corticosteroids.ConclusionsCorticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35331271 · DOI · PMC8944121
Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis [3]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundCerebrotendinous xanthomatosis (CTX) is a rare recessive genetic disease characterized by disruption of bile acid synthesis due to inactivation of the CYP27A1 gene.
- Closing excerpt
- Increased awareness of CTX is important for early diagnosis, which is essential for patients as early treatment significantly slows or prevents disease progression.
- 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 (263 words)
BackgroundCerebrotendinous xanthomatosis (CTX) is a rare recessive genetic disease characterized by disruption of bile acid synthesis due to inactivation of the CYP27A1 gene. Treatment is available in the form of bile acid replacement. CTX is likely underdiagnosed, and prevalence estimates based on case diagnosis are probably inaccurate. Large population-based genomic databases are a valuable resource to estimate prevalence of rare recessive diseases as an orthogonal unbiased approach building upon traditional epidemiological studies.MethodsWe leveraged the Hardy-Weinberg principle and allele frequencies from gnomAD to calculate CTX prevalence. ClinVar and HGMD were used to identify high-confidence pathogenic missense variants and to calculate a disease-specific cutoff. Variant pathogenicity was also assessed by the VarSome implementation of the ACMG/AMP algorithm and the REVEL in silico predictor.ResultsCTX prevalence estimates were highest in Asians (1:44,407-93,084) and lowest in the Finnish population (1:3,388,767). Intermediate estimates were found in Europeans, Americans, and Africans/African Americans (1:70,795-233,597). The REVEL-predicted pathogenic variants accounted for a greater increase in prevalence estimates for Europeans, Americans, and Africans/African Americans compared with Asians. We identified the most frequent alleles designated pathogenic in ClinVar (p.Gly472Ala, p.Arg395Cys), labeled pathogenic based on sequence consequence (p.Met1?), and predicted to be pathogenic by REVEL (p.Met383Lys, p.Arg448His) across populations. Also, we provide a prospective geographic map of estimated disease distribution based on CYP27A1 variation queries performed by healthcare providers from selected specialties.ConclusionsPrevalence estimates calculated herein support and expand upon existing evidence indicating underdiagnosis of CTX, suggesting that improved detection strategies are needed. Increased awareness of CTX is important for early diagnosis, which is essential for patients as early treatment significantly slows or prevents disease progression.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 36650582 · DOI · PMC9843874
Cerebrotendinous xanthomatosis: A complex interplay between a clinically and genetically heterogeneous condition [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Background and purposeCerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease characterized by abnormal bile acid synthesis.
- Closing excerpt
- It emphasizes the importance of a comprehensive approach combining clinical suspicion, imaging, genetic testing and biochemical analyses for accurate diagnosis, interpretation of VUS and management of rare conditions like CTX.
- 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 (237 words)
Background and purposeCerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease characterized by abnormal bile acid synthesis. It often presents with systemic and neurological manifestations; however, atypical presentations can lead to significant diagnostic challenges. This case report highlights the diagnostic complexities and management considerations in a patient with an uncommon presentation of CTX.MethodsWe present a patient with a 25-year history of spastic paraparesis, initially suggestive of hereditary spastic paraplegia (HSP), ultimately diagnosed with CTX associated with a novel CYP27A1 variant of uncertain significance (VUS).ResultsA 53-year-old Greek woman presented with a 25-year history of slowly progressive spastic paraparesis. Initial investigations were largely unremarkable, leading to a presumptive diagnosis of a hereditary spastic paraplegia (HSP)-like syndrome. After 5 years of slow disease progression, the patient developed right ankle swelling. MRI revealed significant enlargement of the Achilles tendon, suggestive of xanthoma infiltration. Subsequent genetic testing identified a homozygous variant of uncertain significance (VUS) in the CYP27A1 gene. Biochemical analyses revealed elevated cholestanol levels and cholestanepentol glucuronide in urine, confirming the diagnosis of CTX. Treatment with chenodeoxycholic acid stabilized her condition over 3 years, but advanced disease limited efficacy in improving disability.ConclusionThis case highlights the diagnostic challenges associated with CTX, stemming from its relative rarity and significant clinical heterogeneity. It emphasizes the importance of a comprehensive approach combining clinical suspicion, imaging, genetic testing and biochemical analyses for accurate diagnosis, interpretation of VUS and management of rare conditions like CTX.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39760285 · DOI · PMC11702487
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 Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management [5]
- Research article Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX) [6]
- Research article Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review [7]
- Research article Necrobiotic xanthogranuloma [8]
- Research article Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene [9]
- Research article Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey [10]
References
- Degos B, Nadjar Y, Amador Mdel M, Lamari F, Sedel F, Roze E, et al.. Natural history of cerebrotendinous xanthomatosis: a paediatric disease diagnosed in adulthood. . 2016. PMID 27084087 · DOI · PMC4833925
- Steinhelfer L, Kühnel T, Jägle H, Mayer S, Karrer S, Haubner F, et al.. Systemic therapy of necrobiotic xanthogranuloma: a systematic review. . 2022. PMID 35331271 · DOI · PMC8944121
- Pramparo T, Steiner RD, Rodems S, Jenkinson C. Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis. . 2023. PMID 36650582 · DOI · PMC9843874
- O'Keefe E, Kiernan M, Huynh W. Cerebrotendinous xanthomatosis: A complex interplay between a clinically and genetically heterogeneous condition. . 2025. PMID 39760285 · DOI · PMC11702487
- Nie S, Chen G, Cao X, Zhang Y. Cerebrotendinous xanthomatosis: a comprehensive review of pathogenesis, clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2014. PMID 25424010 · DOI · PMC4264335
- Salen G, Steiner RD. Epidemiology, diagnosis, and treatment of cerebrotendinous xanthomatosis (CTX). J Inherit Metab Dis. 2017. PMID 28980151 · DOI
- Sivak-Callcott JA, Rootman J, Rasmussen SL, Nugent RA, White VA, Paridaens D, et al.. Adult xanthogranulomatous disease of the orbit and ocular adnexa: new immunohistochemical findings and clinical review. Br J Ophthalmol. 2006. PMID 16622091 · DOI · PMC1857051
- Mehregan DA, Winkelmann RK. Necrobiotic xanthogranuloma. Arch Dermatol. 1992. PMID 1739294 · DOI
- Gallus GN, Dotti MT, Federico A. Clinical and molecular diagnosis of cerebrotendinous xanthomatosis with a review of the mutations in the CYP27A1 gene. Neurol Sci. 2006. PMID 16816916 · DOI
- Pilo-de-la-Fuente B, Jimenez-Escrig A, Lorenzo JR, Pardo J, Arias M, Ares-Luque A, et al.. Cerebrotendinous xanthomatosis in Spain: clinical, prognostic, and genetic survey. Eur J Neurol. 2011. PMID 21645175 · 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 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
See how EvidenceLib is built. Spotted an error? Email support@evidencehelix.com.
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.