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: 3 complete abstracts (523 words), 9 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
Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates.
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: Disease, Lysosomal Storage; Diseases, Lysosomal Storage; Lysosomal Storage Disease; Lysosomal Enzyme Disorders; Disorder, Lysosomal Enzyme; Disorders, Lysosomal Enzyme; Enzyme Disorder, Lysosomal; Enzyme Disorders, Lysosomal.
Where it fits in the MeSH classification
- Broader topics
- Metabolism, Inborn Errors
- Narrower topics
- Aspartylglucosaminuria; Cholesterol Ester Storage Disease; Cystinosis; Lysosomal Storage Diseases, Nervous System; Mannosidase Deficiency Diseases; Mucopolysaccharidoses; Pycnodysostosis
Research landscape
PubMed indexes 32,128 records tagged with the MeSH heading “Lysosomal Storage Diseases” (counts retrieved 2026-10-29). 5,309 of them (16.5%) were published from 2020 onward, and the busiest period so far is through 1999 with 12,481 records.
Reviews account for 4,301 records (13.4%) and meta-analyses for 62. Randomized controlled trials number 181 (0.6%) 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 | 12,481 |
| 2000-2009 | 5,900 |
| 2010-2019 | 8,438 |
| 2020 onward | 5,309 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 4,301 | 13.4% |
| Meta-analyses | 62 | 0.2% |
| Randomized controlled trials | 181 | 0.6% |
Method: PubMed query "Lysosomal Storage Diseases"[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.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Genetic Insights and Diagnostic Challenges in Highly Attenuated Lysosomal Storage Disorders | 2025 | Review article Design not recorded in structured metadata | 10 | cc by PMID 40869962 · DOI · PMC12385809 |
| Mucopolysaccharidoses-What Clinicians Need to Know: A Clinical, Biochemical, and Molecular Overview | 2025 | Review article Design not recorded in structured metadata | 7 | cc by PMID 41154677 · DOI · PMC12562998 |
| Molecular, Metabolic and Inflammatory Patterns Involved in Pathogenesis of Anderson-Fabry Disease | 2026 | Review article Design not recorded in structured metadata | 4 | cc by PMID 41827876 · DOI · PMC12984092 |
Genetic Insights and Diagnostic Challenges in Highly Attenuated Lysosomal Storage Disorders [1]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundLysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters.
- Closing excerpt
- Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members.
- 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 (214 words)
BackgroundLysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities.Objectives/methodsThis study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review.ResultsEnzyme activity, molecular data, and phenotypic assessments are described to explore genotype-phenotype correlations and identify diagnostic challenges.ConclusionsThese findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40869962 · DOI · PMC12385809
Mucopolysaccharidoses-What Clinicians Need to Know: A Clinical, Biochemical, and Molecular Overview [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The classification of mucopolysaccharidoses (MPSs) includes the classical types (I; II; III with subtypes A, B, C, and D; IV with subtypes A and B; VI; VII; IX; X), associated with impaired lysosomal degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs), as a result of deficiency in the specific enzymes responsible for GAG degradation (MPS IIIE has so far been identified only in animal models) and MPS-plus syndrome (MPSPS), which is characterized by an accumulation of undegraded GAGs, arising from impaired endosomal trafficking and inefficient delivery of these compounds to lysosomes (due to the VPS33A protein deficiency with normal GAG-degrading enzyme activities assessed in vitro).
- Closing excerpt
- A brief summary of available and emerging therapies is also presented.
- 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 (136 words)
The classification of mucopolysaccharidoses (MPSs) includes the classical types (I; II; III with subtypes A, B, C, and D; IV with subtypes A and B; VI; VII; IX; X), associated with impaired lysosomal degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs), as a result of deficiency in the specific enzymes responsible for GAG degradation (MPS IIIE has so far been identified only in animal models) and MPS-plus syndrome (MPSPS), which is characterized by an accumulation of undegraded GAGs, arising from impaired endosomal trafficking and inefficient delivery of these compounds to lysosomes (due to the VPS33A protein deficiency with normal GAG-degrading enzyme activities assessed in vitro). The aim of this comprehensive review is to provide physicians with a clinical, biochemical, and molecular overview of MPS manifestation. A brief summary of available and emerging therapies is also presented.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41154677 · DOI · PMC12562998
Molecular, Metabolic and Inflammatory Patterns Involved in Pathogenesis of Anderson-Fabry Disease [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, resulting in deficient α-galactosidase A activity and progressive accumulation of globotriaosylceramide (Gb3) and its derivative lyso-Gb3 within lysosomes.
- Closing excerpt
- A deeper comprehension of these interconnected patterns may guide the development of precision medicine strategies aimed at improving long-term outcomes in Fabry disease.
- 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 (173 words)
Anderson-Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene, resulting in deficient α-galactosidase A activity and progressive accumulation of globotriaosylceramide (Gb3) and its derivative lyso-Gb3 within lysosomes. Beyond substrate storage, FD involves a complex interplay of molecular, metabolic, and inflammatory disturbances that collectively drive multisystemic damage. It seems that Gb3 accumulation impairs autophagic flux, promotes mitochondrial dysfunction, and triggers endoplasmic reticulum stress, leading to oxidative imbalance and bioenergetic failure. Concurrently, activation of innate immune pathways, particularly the TLR4/NF-κB axis, induces pro-inflammatory cytokine release and endothelial dysfunction, while complement activation and adaptive immune responses contribute to chronic inflammation and fibrosis. These mechanisms define a sustained state of "metaflammation," linking lysosomal dysfunction to systemic inflammation. Understanding this molecular cross-talk provides a rationale for identifying novel biomarkers and designing therapies that go beyond enzymatic correction, including chaperone therapy, substrate reduction, and gene-based or anti-inflammatory approaches. A deeper comprehension of these interconnected patterns may guide the development of precision medicine strategies aimed at improving long-term outcomes in Fabry disease.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41827876 · DOI · PMC12984092
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 Classification of GBA1 Variants in Parkinson's Disease: The GBA1-PD Browser [4]
- Research article Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B) [5]
- Research article Fabry disease in infancy and early childhood: a systematic literature review [6]
- Research article Glycogen storage diseases [7]
- Research article Enzyme replacement therapy for Anderson-Fabry disease [8]
- Research article The Bis(monoacylglycero)-phosphate Hypothesis: From Lysosomal Function to Therapeutic Avenues [9]
References
- Urizar E, McCarron EP, Gadepalli C, Bentley A, Woolfson P, Lin S, et al.. Genetic Insights and Diagnostic Challenges in Highly Attenuated Lysosomal Storage Disorders. . 2025. PMID 40869962 · DOI · PMC12385809
- Lipiński P, Różdżyńska-Świątkowska A, Wiśniewska K, Rusecka J, Ługowska A, Żuber Z, et al.. Mucopolysaccharidoses-What Clinicians Need to Know: A Clinical, Biochemical, and Molecular Overview. . 2025. PMID 41154677 · DOI · PMC12562998
- Simonetta I, Baglio I, Tuttolomondo A. Molecular, Metabolic and Inflammatory Patterns Involved in Pathogenesis of Anderson-Fabry Disease. . 2026. PMID 41827876 · DOI · PMC12984092
- Parlar SC, Grenn FP, Kim JJ, Baluwendraat C, Gan-Or Z. Classification of GBA1 Variants in Parkinson's Disease: The GBA1-PD Browser. Mov Disord. 2023. PMID 36598340 · DOI · PMC10033371
- Geberhiwot T, Wasserstein M, Wanninayake S, Bolton SC, Dardis A, Lehman A, et al.. Consensus clinical management guidelines for acid sphingomyelinase deficiency (Niemann-Pick disease types A, B and A/B). Orphanet J Rare Dis. 2023. PMID 37069638 · DOI · PMC10108815
- Laney DA, Peck DS, Atherton AM, Manwaring LP, Christensen KM, Shankar SP, et al.. Fabry disease in infancy and early childhood: a systematic literature review. Genet Med. 2015. PMID 25232851 · DOI
- Hannah WB, Derks TGJ, Drumm ML, Grünert SC, Kishnani PS, Vissing J. Glycogen storage diseases. Nat Rev Dis Primers. 2023. PMID 37679331 · DOI
- El Dib R, Gomaa H, Carvalho RP, Camargo SE, Bazan R, Barretti P, et al.. Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev. 2016. PMID 27454104 · DOI · PMC6481759
- Medoh UN, Abu-Remaileh M. The Bis(monoacylglycero)-phosphate Hypothesis: From Lysosomal Function to Therapeutic Avenues. Annu Rev Biochem. 2024. PMID 38603559 · 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.
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.