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GM1 Gangliosidosis Type 1

GM1 Gangliosidosis Type 1 (Infantile) — Disease Characteristics Research Report

2026-06-13
Falcon MONDO:0009260 Model: Edison Scientific Literature 26 citations

GM1 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

6.3 Suggested GO and CL terms (examples)

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)

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)

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.

Table (click to expand)
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

  1. (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.

  2. (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.

  3. (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.

  4. (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.

  5. (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.

  6. (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.

  7. (NCT04713475 chunk 1): Study of Safety, Tolerability and Efficacy of PBGM01 in Pediatric Participants With GM1 Gangliosidosis. Gemma Biotherapeutics. 2021. ClinicalTrials.gov Identifier: NCT04713475

  8. (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.

  9. (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.

  10. (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.

  11. (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.

  12. (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.

  13. (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

  14. (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.

  15. (NCT04273269 chunk 1): A Safety and Efficacy Study of LYS-GM101 Gene Therapy in Patients With GM1 Gangliosidosis. LYSOGENE. 2021. ClinicalTrials.gov Identifier: NCT04273269

  16. (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.

  17. (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.

  18. (gross2020minimallyinvasiveroutes pages 16-20): AL Gross. Minimally invasive routes ok aav administration to treat gm1 gangliosidosis. Unknown journal, 2020.

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