GM1 Gangliosidosis Type 1
GM1 gangliosidosis type 1 (infantile GM1 gangliosidosis) is an ultra-rare, rapidly progressive neuronopathic lysosomal storage disorder caused by biallelic loss-of-function variants in GLB1 encoding lysosomal beta-galactosidase. Near-absent enzyme activity prevents cleavage of the terminal galactose from GM1 ganglioside, so GM1 ganglioside and other beta-galactose-terminal glycoconjugates accumulate in neurons and somatic tissues. The infantile form presents in early infancy with rapidly progressive neurodegeneration, hepatosplenomegaly, dysostosis multiplex, coarse facial features, and a macular cherry-red spot, with a life expectancy of under 3 years. No FDA-approved disease-modifying therapy exists; AAV-mediated GLB1 gene therapy is in trials.
Ask OpenScientist
Ask a research question about GM1 Gangliosidosis Type 1. OpenScientist will conduct autonomous deep research using the Disorder Mechanisms Knowledge Base and PubMed literature (typically 10-30 minutes).
Do not include personal health information in your question. Questions and results are cached in your browser's local storage.
Mappings
Definitions
1Show evidence (1 reference)
Inheritance
1Show evidence (1 reference)
Pathophysiology
3Show evidence (1 reference)
Show evidence (1 reference)
Show evidence (1 reference)
Pathograph
Phenotypes
6Cardiovascular 2
Show evidence (1 reference)
Show evidence (1 reference)
Head and Neck 1
Show evidence (1 reference)
Musculoskeletal 1
Show evidence (1 reference)
Nervous System 1
Show evidence (1 reference)
Other 1
Show evidence (1 reference)
Genetic Associations
1Show evidence (1 reference)
Medical Actions
2Show evidence (1 reference)
Show evidence (1 reference)
Differential Diagnoses
1Conditions with similar clinical presentations that must be differentiated from GM1 Gangliosidosis Type 1:
- Later symptom onset and a more protracted course with higher residual beta-galactosidase activity.
Show evidence (1 reference)
Source YAML
click to showname: GM1 Gangliosidosis Type 1
creation_date: "2026-06-13T00:00:00Z"
description: >-
GM1 gangliosidosis type 1 (infantile GM1 gangliosidosis) is an ultra-rare, rapidly
progressive neuronopathic lysosomal storage disorder caused by biallelic
loss-of-function variants in GLB1 encoding lysosomal beta-galactosidase. Near-absent
enzyme activity prevents cleavage of the terminal galactose from GM1 ganglioside, so
GM1 ganglioside and other beta-galactose-terminal glycoconjugates accumulate in
neurons and somatic tissues. The infantile form presents in early infancy with rapidly
progressive neurodegeneration, hepatosplenomegaly, dysostosis multiplex, coarse facial
features, and a macular cherry-red spot, with a life expectancy of under 3 years. No
FDA-approved disease-modifying therapy exists; AAV-mediated GLB1 gene therapy is in
trials.
category: Mendelian
disease_term:
preferred_term: GM1 gangliosidosis type 1
term:
id: MONDO:0009260
label: GM1 gangliosidosis type 1
mappings:
mondo_mappings:
- term:
id: MONDO:0009260
label: GM1 gangliosidosis type 1
mapping_predicate: skos:exactMatch
mapping_source: MONDO
mapping_justification: Primary MONDO disease identifier for this infantile GM1 gangliosidosis entry.
synonyms:
- Infantile GM1 gangliosidosis
- GM1 gangliosidosis, type I
- Beta-galactosidase deficiency, infantile
parents:
- Sphingolipidosis
- Lysosomal Storage Disorder
- Neurodegenerative Disease
pathophysiology:
- name: GLB1 Loss of Function and Beta-Galactosidase Deficiency
conforms_to: "lysosomal_substrate_accumulation#Lysosomal Hydrolase or Cofactor Deficiency"
description: >-
Biallelic loss-of-function variants in GLB1 abolish lysosomal beta-galactosidase
activity. The enzyme normally cleaves the terminal beta-1,4-linked galactose from GM1
ganglioside; its loss is the primary biochemical lesion.
gene:
preferred_term: GLB1
term:
id: hgnc:4298
label: GLB1
biological_processes:
- preferred_term: ganglioside catabolic process
modifier: DECREASED
term:
id: GO:0006689
label: ganglioside catabolic process
evidence:
- reference: PMID:33859490
reference_title: "GM1 Gangliosidosis: Mechanisms and Management."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Mutation of the GLB1 gene, which codes for β-gal, prevents cleavage of the terminal β-1,4-linked galactose residue from GM1 ganglioside."
explanation: "GLB1 mutation causes beta-galactosidase deficiency that blocks GM1 ganglioside degradation."
downstream:
- target: Lysosomal GM1 Ganglioside Accumulation in Neurons
description: Loss of enzyme activity allows GM1 ganglioside to accumulate in lysosomes.
- name: Lysosomal GM1 Ganglioside Accumulation in Neurons
conforms_to: "lysosomal_substrate_accumulation#Lysosomal Substrate Accumulation"
description: >-
GM1 ganglioside and other beta-galactose-terminal glycoconjugates accumulate in
neuronal lysosomes (and in somatic tissues), impairing cell physiology.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
cellular_components:
- preferred_term: lysosome
term:
id: GO:0005764
label: lysosome
biological_processes:
- preferred_term: glycosphingolipid metabolic process
modifier: ABNORMAL
term:
id: GO:0006687
label: glycosphingolipid metabolic process
evidence:
- reference: PMID:34539759
reference_title: "GM1 Gangliosidosis-A Mini-Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Absent or reduced β-galactosidase activity leads to the accumulation of β-linked galactose-containing glycoconjugates including the glycosphingolipid (GSL) GM1-ganglioside in neuronal tissue."
explanation: "Beta-galactosidase deficiency causes neuronal GM1 ganglioside accumulation."
downstream:
- target: Neurodegeneration and Multisystem Storage
description: Lysosomal storage impairs neuronal physiology and drives neurodegeneration.
- name: Neurodegeneration and Multisystem Storage
description: >-
Accumulated substrate impairs cell physiology and precipitates progressive dysfunction
of the nervous system, together with somatic (visceral, skeletal) storage pathology.
cell_types:
- preferred_term: neuron
term:
id: CL:0000540
label: neuron
evidence:
- reference: PMID:33859490
reference_title: "GM1 Gangliosidosis: Mechanisms and Management."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Subsequent accumulation of GM1 ganglioside and other substrates in the lysosome impairs cell physiology and precipitates dysfunction of the nervous system."
explanation: "Lysosomal GM1 storage drives nervous-system dysfunction and neurodegeneration."
downstream:
- target: Neurodegeneration
description: Neuronal storage drives progressive neurodegeneration.
- target: Developmental regression
description: Progressive neuronal storage and dysfunction cause loss of acquired developmental milestones.
- target: Hepatosplenomegaly
description: Somatic storage produces visceral organomegaly.
- target: Dysostosis multiplex
description: Somatic lysosomal storage contributes to the skeletal dysplasia/dysostosis multiplex phenotype.
- target: Coarse facial features
description: Somatic storage contributes to coarse facial features.
- target: Cherry red spot of the macula
description: Retinal ganglion-cell storage produces the macular cherry-red spot.
phenotypes:
- name: Neurodegeneration
description: Rapidly progressive neurodegeneration with loss of nervous-system function.
phenotype_term:
preferred_term: Neurodegeneration
term:
id: HP:0002180
label: Neurodegeneration
evidence:
- reference: PMID:33859490
reference_title: "GM1 Gangliosidosis: Mechanisms and Management."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "precipitates dysfunction of the nervous system"
explanation: "Progressive nervous-system dysfunction/neurodegeneration is the core feature."
- name: Developmental regression
description: Loss of acquired developmental milestones in infancy.
phenotype_term:
preferred_term: Developmental regression
term:
id: HP:0002376
label: Developmental regression
evidence:
- reference: PMID:31937438
reference_title: "The natural history of Type 1 infantile GM1 gangliosidosis: A literature-based meta-analysis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "almost all patients experienced significant multi-organ system\ndysfunction and neurodevelopmental regression, particularly in the 6- to\n18-month"
explanation: "Neurodevelopmental regression in the 6-18 month range is near-universal in infantile GM1 gangliosidosis."
- name: Hepatosplenomegaly
description: Visceral organomegaly from somatic storage is characteristic of infantile GM1.
phenotype_term:
preferred_term: Hepatosplenomegaly
term:
id: HP:0001433
label: Hepatosplenomegaly
evidence:
- reference: PMID:31937438
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "infants frequently have accompanying hepatosplenomegaly, skeletal dysplasia, cherry-red maculae, cardiomyopathy, and coarse facial features"
explanation: "Hepatosplenomegaly is a frequent somatic feature of infantile GM1."
- name: Dysostosis multiplex
description: A characteristic constellation of skeletal dysplasia (dysostosis multiplex).
phenotype_term:
preferred_term: Dysostosis multiplex
term:
id: HP:0000943
label: Dysostosis multiplex
evidence:
- reference: PMID:31937438
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "infants frequently have accompanying hepatosplenomegaly, skeletal dysplasia, cherry-red maculae, cardiomyopathy, and coarse facial features"
explanation: "Skeletal dysplasia (dysostosis multiplex) is a frequent somatic feature."
- name: Coarse facial features
description: Coarse facies develop as somatic storage progresses.
phenotype_term:
preferred_term: Coarse facial features
term:
id: HP:0000280
label: Coarse facial features
evidence:
- reference: PMID:31937438
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "infants frequently have accompanying hepatosplenomegaly, skeletal dysplasia, cherry-red maculae, cardiomyopathy, and coarse facial features"
explanation: "Coarse facial features are a frequent somatic feature of infantile GM1."
- name: Cherry red spot of the macula
description: A macular cherry-red spot reflects perifoveal ganglion-cell storage.
phenotype_term:
preferred_term: Cherry red spot of the macula
term:
id: HP:0010729
label: Cherry red spot of the macula
evidence:
- reference: PMID:31937438
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "infants frequently have accompanying hepatosplenomegaly, skeletal dysplasia, cherry-red maculae, cardiomyopathy, and coarse facial features"
explanation: "A cherry-red macula is a frequent ophthalmologic feature of infantile GM1."
inheritance:
- name: Autosomal recessive
inheritance_term:
preferred_term: Autosomal recessive inheritance
term:
id: HP:0000007
label: Autosomal recessive inheritance
evidence:
- reference: PMID:31937438
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "due to biallelic mutations in the GLB1 gene"
explanation: Biallelic GLB1 mutations confirm autosomal recessive inheritance.
genetic:
- name: GLB1
association: Biallelic loss-of-function GLB1 variants causing beta-galactosidase deficiency
relationship_type: CAUSATIVE
variant_origin: GERMLINE
gene_term:
preferred_term: GLB1
term:
id: hgnc:4298
label: GLB1
evidence:
- reference: PMID:34539759
reference_title: "GM1 Gangliosidosis-A Mini-Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "GM1 gangliosidosis is a progressive, neurosomatic, lysosomal storage disorder caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase."
explanation: "GLB1 mutations are the genetic cause of GM1 gangliosidosis."
progression:
- phase: Fatal infantile course
notes: >-
Type 1 GM1 gangliosidosis is rapidly fatal, with a life expectancy under 3 years of age.
evidence:
- reference: PMID:31937438
reference_title: "The natural history of Type 1 infantile GM1 gangliosidosis: A literature-based meta-analysis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Type 1 GM1 gangliosidosis is an ultra-rare, rapidly fatal lysosomal storage disorder, with life expectancy of <3 years of age."
explanation: "Documents the rapidly fatal infantile prognosis."
diagnosis:
- name: Beta-galactosidase enzyme assay
diagnosis_term:
preferred_term: clinical laboratory procedure
term:
id: MAXO:0000006
label: clinical laboratory procedure
description: >-
Demonstration of deficient lysosomal beta-galactosidase activity in leukocytes or
cultured fibroblasts; near-absent activity supports the infantile diagnosis.
markers: Deficient beta-galactosidase activity.
evidence:
- reference: PMID:34539759
reference_title: "GM1 Gangliosidosis-A Mini-Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Absent or reduced β-galactosidase activity leads to the accumulation of β-linked galactose-containing glycoconjugates"
explanation: "Beta-galactosidase activity testing is the biochemical basis of diagnosis."
- name: GLB1 molecular genetic testing
diagnosis_term:
preferred_term: genetic testing
term:
id: MAXO:0000127
label: genetic testing
description: Confirmatory biallelic GLB1 sequencing.
evidence:
- reference: PMID:34539759
reference_title: "GM1 Gangliosidosis-A Mini-Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase"
explanation: "GLB1 sequencing provides molecular confirmation."
differential_diagnoses:
- name: GM1 gangliosidosis type 2
description: >-
The late-infantile/juvenile form of GLB1 deficiency, with later onset and slower
progression than the infantile form.
disease_term:
preferred_term: GM1 gangliosidosis type 2
term:
id: MONDO:0009261
label: GM1 gangliosidosis type 2
distinguishing_features:
- Later symptom onset and a more protracted course with higher residual beta-galactosidase activity.
evidence:
- reference: PMID:31937438
reference_title: "The natural history of Type 1 infantile GM1 gangliosidosis: A literature-based meta-analysis."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Type 2 patients exhibit similar symptoms to Type 1 patients, including psychomotor regression and eye and bone abnormalities, but have an attenuated progression"
explanation: "Type 1 and Type 2 GM1 gangliosidosis are clinically distinguished by onset and course."
treatments:
- name: Supportive Care
description: >-
No FDA-approved disease-modifying therapy exists; management is palliative and
supportive (nutritional, respiratory, seizure, and palliative care).
treatment_term:
preferred_term: Supportive Care
term:
id: NCIT:C15747
label: Supportive Care
evidence:
- reference: PMID:33859490
reference_title: "GM1 Gangliosidosis: Mechanisms and Management."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Beyond palliative and supportive care, no FDA-approved treatments exist for GM1 patients."
explanation: "Care is palliative/supportive in the absence of approved disease-modifying therapy."
- name: Investigational Gene Therapy
description: >-
AAV-mediated GLB1 gene delivery is under investigation in a Phase I/II trial as a
disease-modifying approach.
therapeutic_modality: GENE_THERAPY
treatment_term:
preferred_term: gene therapy
term:
id: MAXO:0001001
label: gene therapy
evidence:
- reference: PMID:33859490
reference_title: "GM1 Gangliosidosis: Mechanisms and Management."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "A Phase I/II clinical trial for GM1 children is ongoing to evaluate the safety and efficacy of adeno-associated virus-mediated GLB1 delivery"
explanation: "AAV-GLB1 gene therapy is in clinical trials for GM1."
definitions:
- name: Clinical case definition of infantile GM1 gangliosidosis
definition_type: CASE_DEFINITION
description: >-
Infantile (type 1) GM1 gangliosidosis is the rapidly progressive neuronopathic form of
GLB1-related beta-galactosidase deficiency, defined by biallelic GLB1 loss-of-function
variants with near-absent enzyme activity, neuronal GM1 ganglioside accumulation, and
a fatal infantile neurodegenerative course.
scope: Disease-level case definition for the severe infantile GM1 gangliosidosis subtype.
evidence:
- reference: PMID:34539759
reference_title: "GM1 Gangliosidosis-A Mini-Review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "GM1 gangliosidosis is a progressive, neurosomatic, lysosomal storage disorder caused by mutations in the GLB1 gene encoding the enzyme β-galactosidase."
explanation: "Anchors the case definition in GLB1/beta-galactosidase deficiency."
References & Deep Research
Deep Research
1GM1 Gangliosidosis Type 1 (Infantile) — Disease Characteristics Research Report
Executive summary
GM1 gangliosidosis type 1 (infantile GM1) is an ultra-rare, rapidly progressive, neuronopathic lysosomal storage disorder caused by biallelic pathogenic variants in GLB1, resulting in β-galactosidase deficiency and accumulation of GM1 ganglioside and other terminal β-galactose–containing glycoconjugates in the CNS and peripheral tissues. Natural history data indicate symptom onset typically in early infancy, diagnosis around late infancy, and death commonly in the second year of life, supporting a narrow therapeutic window for disease-modifying therapies (notably AAV gene therapy) and for newborn screening strategies. (lang2020thenaturalhistory pages 1-2, lang2020thenaturalhistory pages 3-4, lang2020thenaturalhistory pages 6-7)
1. Disease information
1.1 What is the disease?
Type 1 GM1 gangliosidosis is described as an “ultra-rare, rapidly fatal lysosomal storage disorder” with “life expectancy of < 3 years of age.” (Lang et al., Molecular Genetics and Metabolism, available online 30 Dec 2019; publication Mar 2020; URL: https://doi.org/10.1016/j.ymgme.2019.12.012) (lang2020thenaturalhistory pages 1-2)
A mechanistic definition from a 2021 review states: “Mutation of the GLB1 gene, which codes for β-gal, prevents cleavage of the terminal β-1,4-linked galactose residue from GM1 ganglioside. Subsequent accumulation of GM1 ganglioside and other substrates in the lysosome impairs cell physiology and precipitates dysfunction of the nervous system.” (Rha et al., The Application of Clinical Genetics, Apr 2021; URL: https://doi.org/10.2147/TACG.S206076) (rha2021gm1gangliosidosismechanisms pages 1-2)
1.2 Key identifiers (and whether available from tool-retrieved sources)
- MONDO (disease-level resource): GM1 gangliosidosis type 1 MONDO:0009260 (OpenTargets evidence context). (OpenTargets Search: GM1 gangliosidosis)
- MONDO (parent disease): GM1 gangliosidosis MONDO:0018149 (OpenTargets evidence context). (OpenTargets Search: GM1 gangliosidosis)
- OMIM / MIM: MIM#230500 for GM1 gangliosidosis (as used in Lang et al.). (lang2020thenaturalhistory pages 1-2)
- Orphanet, ICD-10/ICD-11, MeSH: Not directly retrievable from the provided tool evidence in this run; thus not asserted here.
1.3 Synonyms and alternative names
Commonly used synonyms across the literature and ClinicalTrials.gov records include: * Infantile GM1 gangliosidosis / Type I GM1 gangliosidosis / early-onset infantile GM1 (arashkaps2019theclinicaland pages 1-2, lang2020thenaturalhistory pages 1-2, NCT04713475 chunk 1) * β-galactosidase-1 (GLB1) deficiency / GLB1 deficiency (NCT04713475 chunk 1)
1.4 Evidence source type
Most disease information here is derived from aggregated disease-level resources and cohorts (meta-analysis and registry-style natural history studies), supplemented by clinical trial registry protocols describing inclusion criteria and endpoints. (lang2020thenaturalhistory pages 1-2, heron2024anaturalhistory pages 1-2, NCT04713475 chunk 1)
2. Etiology
2.1 Disease causal factors
Primary cause (genetic): biallelic pathogenic variants in GLB1 encoding lysosomal β-galactosidase (β-gal; EC 3.2.1.23), causing β-gal deficiency. (lang2020thenaturalhistory pages 1-2, nicoli2021gm1gangliosidosis—aminireview pages 1-2, rha2021gm1gangliosidosismechanisms pages 1-2)
Biochemical consequence: accumulation of GM1 ganglioside, GA1, oligosaccharides, and keratan sulfate due to impaired degradation. (lang2020thenaturalhistory pages 1-2, rha2021gm1gangliosidosismechanisms pages 1-2)
Abstract quote (mechanism): “Absent or reduced β-galactosidase activity leads to the accumulation of β-linked galactose-containing glycoconjugates including the glycosphingolipid (GSL) GM1-ganglioside in neuronal tissue.” (Nicoli et al., Frontiers in Genetics, published 03 Sep 2021; URL: https://doi.org/10.3389/fgene.2021.734878) (nicoli2021gm1gangliosidosis—aminireview pages 1-2)
2.2 Risk factors
For Mendelian infantile GM1, the principal risk factor is inheriting two pathogenic GLB1 alleles (autosomal recessive). Founder effects can increase local incidence. (lang2020thenaturalhistory pages 1-2, rha2021gm1gangliosidosismechanisms pages 1-2)
2.3 Protective factors / gene–environment interaction
No protective environmental factors or gene–environment interactions were directly supported by the retrieved sources in this run; none are asserted.
3. Phenotypes
3.1 Core phenotype (type I) and frequencies
A large literature-based cohort (N=154 type 1) provides frequencies (Table 1). (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3)
Key high-frequency features (Type 1): * Developmental delay / intellectual disability (100%) (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) * Hypotonia (96%) (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) * Dysmorphic/coarse facial features (87%) (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) * Hepatosplenomegaly (85%) (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) * Skeletal abnormalities (dysostosis multiplex/skeletal dysplasia) (82%) (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) * Cherry-red spot (59%) (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) * Seizures (9%; described as later onset, ~10–12 months in the meta-analysis narrative) (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory pages 3-4)
Additional phenotypes noted in summaries include Mongolian spots and cardiomyopathy in some infants. (lang2020thenaturalhistory pages 3-4, lang2020thenaturalhistory pages 1-2)
3.2 Age of onset, severity, progression
Type 1 is the most severe subtype, “traditionally… characterized by an age of first symptom onset between birth and 6 months” and death “often before 3 years.” (lang2020thenaturalhistory pages 1-2)
The meta-analysis reports that a “first symptom onset was often before 3 months of age” and identifies 6–18 months as a period of “significant neurodevelopmental regression and multi-organ system deterioration.” (lang2020thenaturalhistory pages 6-7)
3.3 Quality of life impact
Direct quantitative QoL metrics in type 1 were not found in the retrieved primary texts; however, GM1 type 1 is described as rapidly neurodegenerative with loss/failure to acquire major motor milestones (e.g., crawling/standing/walking), strongly implying profound impact on daily function and caregiving burden. (lang2020thenaturalhistory pages 6-7)
3.4 Suggested HPO terms (examples)
Based on the phenotypes above (frequency-supported where available): * Hypotonia — HP:0001252 (lang2020thenaturalhistory pages 2-3) * Global developmental delay — HP:0001263 (lang2020thenaturalhistory pages 2-3) * Hepatosplenomegaly — HP:0001433 (lang2020thenaturalhistory pages 2-3) * Coarse facial features — HP:0000280 (lang2020thenaturalhistory pages 2-3) * Cherry red spot of the macula — HP:0010729 (lang2020thenaturalhistory pages 2-3) * Seizures — HP:0001250 (lang2020thenaturalhistory pages 2-3) * Skeletal dysplasia / dysostosis multiplex — HP:0002652 (lang2020thenaturalhistory pages 2-3)
4. Genetic / molecular information
4.1 Causal gene(s)
- GLB1 (galactosidase beta 1; β-galactosidase) is the primary causal gene for GM1 gangliosidosis across subtypes. (lang2020thenaturalhistory pages 1-2, nicoli2021gm1gangliosidosis—aminireview pages 1-2, OpenTargets Search: GM1 gangliosidosis)
4.2 Pathogenic variants and variant spectrum
Lang et al. note “Over 165 mutations… reported in the GLB1 gene (ClinVar Database)” and provide type-associated examples: “Common pathogenic mutations associated with Type 1 disease, including p.R59H and c.1622-1627insG…” (lang2020thenaturalhistory pages 1-2)
Nicoli et al. report: “So far 261 pathogenic variants have been described, missense/nonsense mutations being the most prevalent,” with clustering “in exons 2, 6, 15, and 16.” (nicoli2021gm1gangliosidosis—aminireview pages 1-2)
4.3 Functional consequences
The dominant mechanism is loss of function (little or no residual β-gal activity), leading to lysosomal substrate accumulation and downstream neuronal dysfunction/neurodegeneration. (lang2020thenaturalhistory pages 1-2, rha2021gm1gangliosidosismechanisms pages 1-2)
4.4 Modifier genes / epigenetics / chromosomal abnormalities
No specific modifier genes, epigenetic signatures, or chromosomal abnormalities were supported by the retrieved evidence in this run.
4.5 Suggested ontology terms
- GO (biological process): lysosomal catabolic process (GO:0007040), sphingolipid metabolic process (GO:0006665), glycosaminoglycan catabolic process (GO:0006027)
- GO (cellular component): lysosome (GO:0005764)
(These are suggested based on the described lysosomal enzyme deficiency and substrate accumulation; the sources establish lysosomal dysfunction and substrate buildup but do not explicitly list GO terms.) (rha2021gm1gangliosidosismechanisms pages 1-2, lang2020thenaturalhistory pages 1-2)
5. Environmental information
No environmental, lifestyle, or infectious etiologies were supported by the retrieved evidence for this Mendelian disorder.
6. Mechanism / pathophysiology
6.1 Causal chain (upstream → downstream)
1) Biallelic GLB1 pathogenic variants → 2) β-galactosidase deficiency → 3) accumulation of GM1 ganglioside/GA1 and other β-galactose–terminal substrates in lysosomes (especially in neurons) → 4) impaired cellular physiology and neurodegeneration, with multisystem involvement (liver/spleen, skeleton, heart). (rha2021gm1gangliosidosismechanisms pages 1-2, lang2020thenaturalhistory pages 1-2)
6.2 Pathways / processes implicated
- Lysosomal glycosphingolipid degradation (GM1/GA1) and keratan sulfate catabolism are central biochemical pathways. (lang2020thenaturalhistory pages 1-2, NCT04713475 chunk 1)
- Pathophysiology is constrained by the blood–brain barrier for therapies (important for treatment design). (foster2024therapeuticdevelopmentsfor pages 2-4)
6.3 Suggested GO and CL terms (examples)
- GO processes: lysosomal lumen acid hydrolase activity–related pathways; neuronal cell death (GO:0070997) (suggested; neurodegeneration is supported but specific GO annotations not directly extracted). (lang2020thenaturalhistory pages 1-2)
- CL cell types (suggested): neuron (CL:0000540), astrocyte (CL:0000127), microglial cell (CL:0000129), based on CNS storage/neurodegeneration framing. (lang2020thenaturalhistory pages 1-2, rha2021gm1gangliosidosismechanisms pages 1-2)
7. Anatomical structures affected
7.1 Organ and system involvement
Type 1 involves: * Central nervous system (neuronopathic neurodegeneration) (lang2020thenaturalhistory pages 1-2) * Hepatosplenomegaly (liver/spleen involvement) (lang2020thenaturalhistory pages 2-3) * Skeletal system (skeletal dysplasia/dysostosis multiplex) (lang2020thenaturalhistory pages 2-3) * Eye (cherry-red maculae) (lang2020thenaturalhistory pages 2-3) * Heart (cardiomyopathy noted as frequent accompanying sign in infants) (lang2020thenaturalhistory pages 1-2)
7.2 Suggested UBERON terms (examples)
- Brain — UBERON:0000955 (lang2020thenaturalhistory pages 1-2)
- Liver — UBERON:0002107 (lang2020thenaturalhistory pages 2-3)
- Spleen — UBERON:0002106 (lang2020thenaturalhistory pages 2-3)
- Skeleton/bone — UBERON:0002481 (lang2020thenaturalhistory pages 2-3)
- Retina/macula — UBERON:0000966 (for macular cherry-red spot phenotype) (lang2020thenaturalhistory pages 2-3)
8. Temporal development
8.1 Onset
In a type 1 cohort (N=154), mean age of first symptom onset was 2.8 months (median 2.5; range 0–11). (lang2020thenaturalhistory pages 3-4)
8.2 Progression and milestones
The meta-analysis highlights a “predictable clinical course,” with marked regression/deterioration in 6–18 months, and failure to attain later milestones (crawling/standing/walking). (lang2020thenaturalhistory pages 6-7)
8.3 Duration
Mean age at death in the meta-analysis was 18.9 months (median 20.0; range 2–35). (lang2020thenaturalhistory pages 3-4)
9. Inheritance and population
9.1 Inheritance
Autosomal recessive inheritance is consistently described (biallelic GLB1 mutations). (lang2020thenaturalhistory pages 1-2, NCT04713475 chunk 1)
9.2 Epidemiology (statistics)
- Incidence estimates: “reported to be 1 in 100,000–200,000 live births,” with higher incidence in founder populations. (lang2020thenaturalhistory pages 1-2)
- A 2019 clinical series similarly states: “The overall incidence… is estimated to be 1:100 000–1:200 000 live births worldwide.” (Arash-Kaps et al., J Pediatr, Dec 2019; URL: https://doi.org/10.1016/j.jpeds.2019.08.016) (arashkaps2019theclinicaland pages 1-2)
9.3 Founder effects and high-incidence populations
A 2021 review reports markedly elevated incidence/carrier rates in specific populations (e.g., Malta; Roma; Cyprus/Pelendri). (rha2021gm1gangliosidosismechanisms pages 1-2)
10. Diagnostics
10.1 Clinical/biochemical tests
Enzyme assay: In a 22-patient cohort, “Residual β-galactosidase activity was measured in leucocytes… and in fibroblasts… using the artificial 4-methylumbelliferyl-β-galactopyranoside as substrate.” (Arash-Kaps et al., Dec 2019; URL: https://doi.org/10.1016/j.jpeds.2019.08.016) (arashkaps2019theclinicaland pages 1-2)
Supportive screening labs (reported abnormal proportions in that cohort): increased ASAT (13/20), chitotriosidase (12/15), pathologic urinary oligosaccharides (10/19). (arashkaps2019theclinicaland pages 1-2)
10.2 Genetic testing
Sanger sequencing of GLB1 was used in the 2019 cohort: “In 20 of 22 patients, molecular analysis of the GLB1 gene was performed… by Sanger sequencing.” (arashkaps2019theclinicaland pages 1-2)
Clinical trials specify diagnosis confirmation via genotyping (biallelic GLB1 mutations) and documented β-gal deficiency in a CLIA-certified laboratory for eligibility. (NCT03952637 chunk 1, NCT04713475 chunk 1)
10.3 Biomarkers (including recent 2023–2024 developments)
Pentasaccharide H3N2b (pharmacodynamic biomarker; 2023): * Abstract quote: “We identified two pentasaccharide biomarkers, H3N2a and H3N2b, that were elevated more than 18-fold in patient plasma, cerebrospinal fluid (CSF), and urine.” (Kell et al., eBioMedicine, published online 31 May 2023; Jun 2023; URL: https://doi.org/10.1016/j.ebiom.2023.104627) (kell2023apentasaccharidefor pages 1-2) * Abstract quote (treatment monitoring): “Following intravenous (IV) AAV9 gene therapy treatment, reduction of H3N2b was observed…” and “Reduction of H3N2b accurately reflected normalization of neuropathology… and improvement of clinical outcomes…” (kell2023apentasaccharidefor pages 1-2)
Trial-integrated biomarkers (gene therapy trials): ClinicalTrials.gov endpoints for PBGM01 include NfL in plasma/CSF, MRI measures, and ventilator-free survival (vs natural history). (NCT04713475 chunk 1)
10.4 Neuroimaging and functional testing (trial-based implementation)
The NIH AAV9-GLB1 trial protocol includes baseline and longitudinal testing: MRI/MRS/fMRI, EEG, skeletal survey, ophthalmology exam, modified barium swallow, echocardiogram/EKG, and others. (NCT03952637 chunk 1)
10.5 Newborn screening
The type 1 meta-analysis explicitly suggests improved diagnostic timing via “Implementation of newborn screening and increased use of whole exome sequencing.” (lang2020thenaturalhistory pages 6-7)
11. Outcome / prognosis
11.1 Natural history timing and survival (key statistics)
From the type 1 meta-analysis (N=154): * Mean age at diagnosis 8.7 months (lang2020thenaturalhistory pages 1-2) * Mean age at death 18.9 months (lang2020thenaturalhistory pages 1-2) * Survival distribution: “96% of patients are alive before 12 months” and “more than half of patients die between 12 and 24 months.” (lang2020thenaturalhistory pages 6-7)
From the large RETRIEVE natural history study (early-onset GM1; includes infantile presentations): * “In Group A, median (95% CI) survival was 19.0 (18.0, 22.0) months in patients with GM1.” (Héron et al., Orphanet J Rare Dis, Dec 2024; URL: https://doi.org/10.1186/s13023-024-03409-1) (heron2024anaturalhistory pages 1-2)
11.2 Prognostic factors
Earlier onset is associated with more rapid progression (concept supported in type I definition and natural history patterns), but specific quantitative prognostic models were not extracted from retrieved texts in this run. (lang2020thenaturalhistory pages 1-2, lang2020thenaturalhistory pages 6-7)
12. Treatment
12.1 Current standard of care (real-world implementation)
No approved disease-modifying therapy is documented in the retrieved sources; care is “limited to symptomatic supportive care.” (lang2020thenaturalhistory pages 1-2)
Supportive approaches referenced include seizure control and feeding/airway interventions. (rha2021gm1gangliosidosismechanisms pages 1-2)
Suggested MAXO terms (examples): * Supportive care — MAXO:0000147 (suggested) * Anticonvulsant therapy — MAXO term for antiseizure medication (suggested) * Gastrostomy tube feeding — MAXO:0000647 (suggested)
12.2 Advanced therapeutics / clinical trials (with NCT identifiers)
AAV9-GLB1 (intravenous) — NIH Phase 1/2
- ClinicalTrials.gov: “A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis” — NCT03952637. Start date 2019-08-19; status Recruiting (as of 2025-12 update). (NCT03952637 chunk 1)
- Route: intravenous infusion; vector: AAV9/GLB1. (NCT03952637 chunk 1)
PBGM01 (AAVhu68-GLB1; cisterna magna) — Imagine-1
- ClinicalTrials.gov: “Phase 1/2… PBGM01 delivered into the cisterna magna… Type 1 and Type 2a infantile GM1” — NCT04713475. Start date 2021-03-17; status Active not recruiting (as of 2025-05 update). (NCT04713475 chunk 1)
- Primary outcomes include treatment-related AEs/SAEs (CTCAE v5.0) up to 5 years and Bayley developmental milestones change through 2 years. (NCT04713475 chunk 1)
- Secondary outcomes include biomarkers of β-gal activity/substrates, NfL, MRI, QoL scales, and ventilator-free survival compared with natural history. (NCT04713475 chunk 1)
LYS-GM101 (AAVrh.10-GLB1; intracisternal)
- ClinicalTrials.gov: NCT04273269; status Terminated (closure not due to safety; cessation of activities). (NCT04273269 chunk 1)
- Intervention: AAVrh.10 carrying human β-galactosidase cDNA; single intracisternal injection; secondary outcomes included motor function, MRI, developmental scales, and β-gal/GM1 biomarkers in blood and CSF. (NCT04273269 chunk 1)
12.3 Substrate reduction therapy (SRT)
A 2024 review summarizes limited clinical experience with miglustat and notes a U.S. infantile GM1 trial (NCT02030015) was unsuccessful with high mortality; efficacy for type 1 remains unproven in the retrieved text. (foster2024therapeuticdevelopmentsfor pages 5-6)
A mini-review notes that a trial using a glucosylceramide synthase inhibitor venglustat is recruiting type II and III patients (not type I). (nicoli2021gm1gangliosidosis—aminireview pages 1-2)
12.4 Recent research developments (prioritizing 2023–2024)
Biomarker advancement (2023): H3N2b pentasaccharide validated as a pharmacodynamic biomarker for monitoring response to gene therapy, including evidence of reduction in treated cats and a treated patient. (kell2023apentasaccharidefor pages 1-2)
Natural history dataset expansion (2024): RETRIEVE provides one of the larger early-onset GM1 survival datasets with median survival and a multi-country cohort design, intended to support future trials and historical controls. (heron2024anaturalhistory pages 1-2)
13. Prevention
13.1 Primary prevention
For an autosomal recessive disorder, prevention primarily involves carrier screening, reproductive counseling, and prenatal/preimplantation testing, but specific guideline documents were not retrieved in this run.
13.2 Secondary prevention (early detection)
The type 1 natural history meta-analysis explicitly argues for improved public awareness/screening and mentions “Implementation of newborn screening.” (lang2020thenaturalhistory pages 6-7)
14. Other species / natural disease
Naturally occurring GM1 has been documented in multiple species, particularly as translational large-animal models: * Feline GM1 gangliosidosis (natural model used extensively for AAV gene therapy and biomarker work) (rha2021gm1gangliosidosismechanisms pages 21-21) * Ovine (sheep) GM1 (natural model) (rha2021gm1gangliosidosismechanisms pages 21-21) * Additional species reported in a model-focused source include dogs, calves, and sheep. (gross2020minimallyinvasiveroutes pages 16-20)
15. Model organisms
15.1 Mouse models
A mini-review states: “There are five mouse models of GM1-gangliosidosis… [that] share the major abnormalities and neurological symptoms that are characteristic of the most severe forms of GM1-gangliosidosis,” and have been used “to study pathogenic mechanisms, to identify biomarkers, and to evaluate therapeutic strategies.” (nicoli2021gm1gangliosidosis—aminireview pages 1-2)
15.2 Feline (cat) model
A 2021 review notes feline GM1 has been used for intracranial gene therapy with “sustained normalization of neurological disease” and for identifying “novel biomarkers… [that] reflect the clinical efficacy of gene therapy.” (rha2021gm1gangliosidosismechanisms pages 21-21)
15.3 Model limitations
A model-focused source argues murine models are invaluable but do not fully recapitulate human disease because of differences in lifespan, body/brain size, and cerebral complexity. (gross2020minimallyinvasiveroutes pages 16-20)
Evidence tables and compact reference
The following artifact consolidates key identifiers, natural history statistics, and phenotype frequencies.
| Item | Value | Evidence/source (with citation IDs) | URL (if in evidence) |
|---|---|---|---|
| Disease name | GM1 gangliosidosis type 1 | OpenTargets disease association lists “GM1 gangliosidosis type 1” with MONDO_0009260; clinical literature describes Type 1 as the infantile form (OpenTargets Search: GM1 gangliosidosis, nicoli2021gm1gangliosidosis—aminireview pages 1-2, lang2020thenaturalhistory pages 1-2) | https://platform.opentargets.org |
| MONDO ID | MONDO:0009260 | OpenTargets context for “GM1 gangliosidosis type 1” (OpenTargets Search: GM1 gangliosidosis) | https://platform.opentargets.org |
| OMIM / MIM | MIM #230500 | Lang 2020 introduction: “GM1 gangliosidosis (MIM# 230500)” (lang2020thenaturalhistory pages 1-2) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Key causal gene | GLB1 (galactosidase beta 1) | GM1 is caused by biallelic GLB1 mutations causing β-galactosidase deficiency (nicoli2021gm1gangliosidosis—aminireview pages 1-2, lang2020thenaturalhistory pages 1-2, rha2021gm1gangliosidosismechanisms pages 1-2) | https://doi.org/10.3389/fgene.2021.734878 |
| Common synonyms | Infantile GM1 gangliosidosis; Type I GM1 gangliosidosis; early onset infantile GM1 gangliosidosis; GLB1 deficiency | Sources classify disease as Type I/infantile and note “GLB1 deficiency” as a condition label (NCT04713475 chunk 1, nicoli2021gm1gangliosidosis—aminireview pages 1-2, arashkaps2019theclinicaland pages 1-2) | https://clinicaltrials.gov/study/NCT04713475 |
| Short definition | Progressive neuronopathic lysosomal storage disorder caused by β-galactosidase deficiency, leading to accumulation of GM1 ganglioside and other β-linked galactose-containing substrates; infantile/type I is the most severe form | Review and mini-review definitions (nicoli2021gm1gangliosidosis—aminireview pages 1-2, lang2020thenaturalhistory pages 1-2, rha2021gm1gangliosidosismechanisms pages 1-2) | https://doi.org/10.2147/TACG.S206076 |
| Mean age at first symptom onset | 2.8 months (median 2.5; range 0–11) | Literature-based meta-analysis of 154 Type 1 cases (lang2020thenaturalhistory pages 3-4) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Mean age at first hospital admission | 6.3 months (median 6.0; range 0–24) | Lang 2020 natural history meta-analysis (lang2020thenaturalhistory pages 3-4) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Mean age at diagnosis | 8.7 months (median 8.0; range 0–30) | Lang 2020 reports “average age of diagnosis was 8.7 months” (lang2020thenaturalhistory pages 1-2, lang2020thenaturalhistory pages 3-4) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Diagnostic delay from first symptoms | 5.9 months | Lang 2020 meta-analysis (lang2020thenaturalhistory pages 3-4) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Mean age at death | 18.9 months (median 20.0; range 2–35) | Lang 2020 reports “average age of death was 18.9 months” (lang2020thenaturalhistory pages 1-2, lang2020thenaturalhistory pages 3-4) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Survival pattern | 96% alive before 12 months; >50% die between 12 and 24 months; life expectancy <3 years | Lang 2020 and review summary (lang2020thenaturalhistory pages 6-7, lang2020thenaturalhistory pages 1-2) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Median survival in early-onset GM1 cohort | 19.0 months (95% CI 18.0–22.0) | RETRIEVE natural history study, Group A, 60 GM1 patients (heron2024anaturalhistory pages 1-2) | https://doi.org/10.1186/s13023-024-03409-1 |
| Developmental delay / mental retardation frequency | 100% | Lang 2020 Table 1, Type 1 frequency summary (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Hypotonia frequency | 96% | Lang 2020 Table 1, Type 1 frequency summary (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Dysmorphic / coarse facial features frequency | 87% | Lang 2020 Table 1, Type 1 frequency summary (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Hepatosplenomegaly frequency | 85% | Lang 2020 Table 1, Type 1 frequency summary (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Skeletal abnormalities frequency | 82% | Lang 2020 Table 1, Type 1 frequency summary (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Cherry-red spot frequency | 59% | Lang 2020 Table 1, Type 1 frequency summary (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory media 45298dc3) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
| Seizure frequency | 9% | Lang 2020 Table 1, Type 1 frequency summary; later onset around 10–12 months noted in meta-analysis (lang2020thenaturalhistory pages 2-3, lang2020thenaturalhistory pages 3-4) | https://doi.org/10.1016/j.ymgme.2019.12.012 |
Table: This table condenses identifiers, nomenclature, core definition, key natural-history statistics, and major phenotype frequencies for GM1 gangliosidosis type 1 (infantile). It is useful as a compact evidence-backed reference for disease knowledge base population.
Notes on gaps vs requested template
- ICD-10/ICD-11, Orphanet IDs, and MeSH terms were not available in the retrieved evidence and thus are not reported.
- Some requested elements (e.g., formal diagnostic criteria, validated QoL instruments in type 1 cohorts, modifier genes, epigenetics) were not supported by tool-retrieved primary sources in this run.
References
-
(lang2020thenaturalhistory pages 1-2): Frederick M. Lang, Paul Korner, Mark Harnett, Ajith Karunakara, and Cynthia J. Tifft. The natural history of type 1 infantile gm1 gangliosidosis: a literature-based meta-analysis. Mar 2020. URL: https://doi.org/10.1016/j.ymgme.2019.12.012, doi:10.1016/j.ymgme.2019.12.012. This article has 54 citations and is from a peer-reviewed journal.
-
(lang2020thenaturalhistory pages 3-4): Frederick M. Lang, Paul Korner, Mark Harnett, Ajith Karunakara, and Cynthia J. Tifft. The natural history of type 1 infantile gm1 gangliosidosis: a literature-based meta-analysis. Mar 2020. URL: https://doi.org/10.1016/j.ymgme.2019.12.012, doi:10.1016/j.ymgme.2019.12.012. This article has 54 citations and is from a peer-reviewed journal.
-
(lang2020thenaturalhistory pages 6-7): Frederick M. Lang, Paul Korner, Mark Harnett, Ajith Karunakara, and Cynthia J. Tifft. The natural history of type 1 infantile gm1 gangliosidosis: a literature-based meta-analysis. Mar 2020. URL: https://doi.org/10.1016/j.ymgme.2019.12.012, doi:10.1016/j.ymgme.2019.12.012. This article has 54 citations and is from a peer-reviewed journal.
-
(rha2021gm1gangliosidosismechanisms pages 1-2): Allisandra K. Rha, Anne S. Maguire, and Douglas R. Martin. Gm1 gangliosidosis: mechanisms and management. The Application of Clinical Genetics, 14:209-233, Apr 2021. URL: https://doi.org/10.2147/tacg.s206076, doi:10.2147/tacg.s206076. This article has 96 citations.
-
(OpenTargets Search: GM1 gangliosidosis): Open Targets Query (GM1 gangliosidosis, 9 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
-
(arashkaps2019theclinicaland pages 1-2): Laila Arash-Kaps, Katalin Komlosi, Marlene Seegräber, Stefan Diederich, Eduard Paschke, Yasmina Amraoui, Skadi Beblo, Andrea Dieckmann, Martin Smitka, and Julia B. Hennermann. The clinical and molecular spectrum of gm1 gangliosidosis. The Journal of Pediatrics, 215:152-157.e3, Dec 2019. URL: https://doi.org/10.1016/j.jpeds.2019.08.016, doi:10.1016/j.jpeds.2019.08.016. This article has 49 citations.
-
(NCT04713475 chunk 1): Study of Safety, Tolerability and Efficacy of PBGM01 in Pediatric Participants With GM1 Gangliosidosis. Gemma Biotherapeutics. 2021. ClinicalTrials.gov Identifier: NCT04713475
-
(heron2024anaturalhistory pages 1-2): Bénédicte Héron, Spyros Batzios, Eugen Mengel, Roberto Giugliani, Marc Patterson, Matthias Gautschi, Peter Cornelisse, Luba Trokan, Barbara Schwierin, and Marianne Rohrbach. A natural history study of pediatric patients with early onset of gm1 gangliosidosis, gm2 gangliosidoses, or gaucher disease type 2 (retrieve). Orphanet Journal of Rare Diseases, Dec 2024. URL: https://doi.org/10.1186/s13023-024-03409-1, doi:10.1186/s13023-024-03409-1. This article has 2 citations and is from a peer-reviewed journal.
-
(nicoli2021gm1gangliosidosis—aminireview pages 1-2): Elena-Raluca Nicoli, Ida Annunziata, Alessandra d’Azzo, Frances M. Platt, Cynthia J. Tifft, and Karolina M. Stepien. Gm1 gangliosidosis—a mini-review. Frontiers in Genetics, Sep 2021. URL: https://doi.org/10.3389/fgene.2021.734878, doi:10.3389/fgene.2021.734878. This article has 107 citations and is from a peer-reviewed journal.
-
(lang2020thenaturalhistory pages 2-3): Frederick M. Lang, Paul Korner, Mark Harnett, Ajith Karunakara, and Cynthia J. Tifft. The natural history of type 1 infantile gm1 gangliosidosis: a literature-based meta-analysis. Mar 2020. URL: https://doi.org/10.1016/j.ymgme.2019.12.012, doi:10.1016/j.ymgme.2019.12.012. This article has 54 citations and is from a peer-reviewed journal.
-
(lang2020thenaturalhistory media 45298dc3): Frederick M. Lang, Paul Korner, Mark Harnett, Ajith Karunakara, and Cynthia J. Tifft. The natural history of type 1 infantile gm1 gangliosidosis: a literature-based meta-analysis. Mar 2020. URL: https://doi.org/10.1016/j.ymgme.2019.12.012, doi:10.1016/j.ymgme.2019.12.012. This article has 54 citations and is from a peer-reviewed journal.
-
(foster2024therapeuticdevelopmentsfor pages 2-4): Dorian Foster, Lucian Williams, Noah Arnold, and Jessica Larsen. Therapeutic developments for neurodegenerative gm1 gangliosidosis. Frontiers in Neuroscience, Apr 2024. URL: https://doi.org/10.3389/fnins.2024.1392683, doi:10.3389/fnins.2024.1392683. This article has 21 citations and is from a peer-reviewed journal.
-
(NCT03952637 chunk 1): A Phase 1/2 Study of Intravenous Gene Transfer With an AAV9 Vector Expressing Human Beta-galactosidase in Type I and Type II GM1 Gangliosidosis. National Human Genome Research Institute (NHGRI). 2019. ClinicalTrials.gov Identifier: NCT03952637
-
(kell2023apentasaccharidefor pages 1-2): Pamela Kell, Rohini Sidhu, Mingxing Qian, Sonali Mishra, Elena-Raluca Nicoli, Precilla D'Souza, Cynthia J. Tifft, Amanda L. Gross, Heather L. Gray-Edwards, Douglas R. Martin, Miguel Sena- Esteves, Dennis J. Dietzen, Manmilan Singh, Jingqin Luo, Jean E. Schaffer, Daniel S. Ory, and Xuntian Jiang. A pentasaccharide for monitoring pharmacodynamic response to gene therapy in gm1 gangliosidosis. Jun 2023. URL: https://doi.org/10.1016/j.ebiom.2023.104627, doi:10.1016/j.ebiom.2023.104627. This article has 19 citations and is from a peer-reviewed journal.
-
(NCT04273269 chunk 1): A Safety and Efficacy Study of LYS-GM101 Gene Therapy in Patients With GM1 Gangliosidosis. LYSOGENE. 2021. ClinicalTrials.gov Identifier: NCT04273269
-
(foster2024therapeuticdevelopmentsfor pages 5-6): Dorian Foster, Lucian Williams, Noah Arnold, and Jessica Larsen. Therapeutic developments for neurodegenerative gm1 gangliosidosis. Frontiers in Neuroscience, Apr 2024. URL: https://doi.org/10.3389/fnins.2024.1392683, doi:10.3389/fnins.2024.1392683. This article has 21 citations and is from a peer-reviewed journal.
-
(rha2021gm1gangliosidosismechanisms pages 21-21): Allisandra K. Rha, Anne S. Maguire, and Douglas R. Martin. Gm1 gangliosidosis: mechanisms and management. The Application of Clinical Genetics, 14:209-233, Apr 2021. URL: https://doi.org/10.2147/tacg.s206076, doi:10.2147/tacg.s206076. This article has 96 citations.
-
(gross2020minimallyinvasiveroutes pages 16-20): AL Gross. Minimally invasive routes ok aav administration to treat gm1 gangliosidosis. Unknown journal, 2020.
