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GM2 gangliosidosis - Clinical Profile, Genes & Research | Kisho | Kisho

Rare Disease

GM2 gangliosidosis

MONDO:0017720

Also known as:GM>2< gangliosidosisgangliosidosis GM2GM2-gangliosidosis, B, B1, AB variant

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Overview

A group of recessively inherited diseases characterized by the intralysosomal accumulation of G(M2) GANGLIOSIDE in the neuronal cells. Subtypes include mutations of enzymes in the BETA-N-ACETYLHEXOSAMINIDASES system or G(M2) ACTIVATOR PROTEIN leading to disruption of normal degradation of GANGLIOSIDES, a subclass of ACIDIC GLYCOSPHINGOLIPIDS.

OnsetINFANTILE

TreatmentsNo approved treatments · 6 in pipeline

Clinical Trials8 registered · 5 recruiting

Clinical Presentation

Built from Human Phenotype Ontology (HPO) phenotype annotations and GeneReviews clinical descriptions. Features represent findings documented across known cases — not an exhaustive list of possible symptoms.

No HPO annotations are available for this condition.

Age of onset: infancy.

GeneReviews

Clinical Guidance

Acute infantile GM2 activator deficiency is a neurodegenerative disorder in which infants, who are generally normal at birth, have progressive weakness and slowing of developmental progress between ages four and 12 months. An ensuing developmental plateau is followed by progressively rapid developmental regression. By the second year of life decerebrate posturing, difficulty in swallowing, and worsening seizures lead to an unresponsive vegetative state. Death usually occurs between ages two and three years. To date, 13 individuals have been reported with acute infantile GM2 activator deficiency [, , , , , , , , , , , ]. The following description of the phenotypic features associated with acute infantile GM2 activator deficiency is based on these reports. Table 2. Acute Infantile GM2 Activator Deficiency: Frequency of Select Features

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

No consensus clinical diagnostic criteria for GM2 activator deficiency have been published.

Suggestive Findings

GM2 activator deficiency should be suspected in children with the following clinical and imaging findings and family history.

Clinical findings

• Neurologic

Progressive weakness or loss of motor skills beginning between ages four to 12 months

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for GM2 gangliosidosis. An additional 6 compounds hold orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for GM2 gangliosidosis, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for GM2 gangliosidosis. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

There are no formal guidelines for surveillance for individuals with acute infantile GM2 activator deficiency. provides suggestions for periodic evaluations to monitor existing disease manifestations and to identify new manifestations requiring modification of supportive care.

Table 6.

Recommended Surveillance for Individuals with Acute Infantile GM2 Activator Deficiency

System/Concern | Evaluation | Frequency

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

8 clinical trials registered, 5 recruiting. Interventions under study include drug therapy, other interventions, and biologic therapy. Pipeline includes 1 PHASE3, 2 PHASE2, 1 PHASE1. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT03333200](https://clinicaltrials.gov/study/NCT03333200)

Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 6:55 PM UTC

MONDOHPOClinicalTrials.govFDAPubMedHGNCClinVarClinGenGeneReviewsOrphanetOMIMRUSP

Medical References

External Resources

Orphanet

European rare disease database

Orphanet:309152

GARD

Genetic and Rare Diseases Info Center

GARD:21323

Questions for Your Care Team

→Are any of the 8 active clinical trials a good fit for my situation?
→With 6 compounds in the orphan drug pipeline, which are furthest along in development and which clinical trials should I be aware of?
→Are there specialists or centers of excellence for this condition in my area?
→Is there a patient registry I should consider joining?

← Back to All Diseases

Feature	# of Personsw/Feature	Comment
Developmental delay	13	—
Cherry-red macula	13	—
Hypotonia	12	Tone not specifically discussed in 13th case is likely present in all affected persons. While axial tone is universally , limb tone may be or .
Seizures	9	—
Exaggerated startle response	8	—
Hyperreflexia	4	Hyperreflexia was present in all reports in which reflexes were specifically discussed.
Hepatomegaly	2	Affected infants are generally normal at birth. Progressive weakness, exaggerated startle, and slowing of developmental progress is typically noted between ages four to 12 months.

GeneReviews

Differential Diagnosis

Table 3. Genetic Disorders of Interest in the Differential Diagnosis of Acute Infantile GM2 Activator Deficiency

Gene	DiffDx Disorder1	Clinical Features of DiffDx Disorder
Cherry-red macula (≤12 mos)	Onset of neurologic regression	Other features/ Comments
≤6 mos	Macrocephaly, head lag, hypotonia, seizures	Leukoencephalopathy CLN5 CLN6 CLN8 CTSD MFSD8 PPT1 TPP1
≤6 mos	Visual deficits, seizures	Abnormal ERG
CTSA	Galactosialidosis (OMIM 256540)	+
≤6 mos	Seizures	Leukodystrophy, peripheral neuropathy, irritability
GBA1 (GBA)	Gaucher disease type 2	—
≤6 mos	Seizures in some persons	Oculomotor abnormalities, hypertonia, opisthotonos; ichthyosiform or collodion skin changes may be seen in persons w/severe involvement.
GFAP	Alexander disease, infantile form	—
≤6 mos	Macrocephaly, seizures	Leukodystrophy
GLB1	GM1 gangliosidosis type 1 (See GLB1 Disorders.)	+
GNPTAB	Mucolipidosis II (I-cell disease) (See GNPTAB Disorders.)	≤12 mos
HEXA	Tay-Sachs disease (See HEXA Disorders.)	+
Sandhoff disease	+	≤6 mos
NEU1	Sialidosis type II (OMIM 256550)	+
SMPD1	Niemann-Pick disease type A (See Acid Sphingomyelinase Deficiency.)	+

Source: GeneReviews — "GM2 Activator Deficiency"

GeneReviews

Management Guidelines

No clinical practice guidelines for acute infantile GM2 activator deficiency have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with acute infantile GM2 activator deficiency, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Acute Infantile GM2 Activator Deficiency

System/Concern	Evaluation	Comment
Neurologic	Neurology eval	To incl brain MRI; Consider EEG if seizures are a concern. Musculoskeletal
system	Physical medicine rehab/ PT OT eval	To incl assessment of:; Gross motor fine motor skills; Need for adaptive devices; Need for PT (to prevent deformities) Gastrointestinal/
Feeding	Gastroenterology/ nutrition/ feeding team eval	To incl swallow study for eval of aspiration risk nutritional status; Consider eval for gastrostomy tube placement in those w/dysphagia /or aspiration risk.; Assess for constipation.
Eyes	Ophthalmologic exam	Eval for macular degeneration, cherry-red macula, visual loss
Respiratory	Evaluate for aspiration risk.	Assess need for airway hygiene. Genetic
counseling	By genetics professionals1	To obtain a pedigree inform affected persons families re nature, MOI, implications of this disorder to facilitate medical personal decision making Family support resources
Ethics consultation	Clinical ethics services	Assess health care decisions in context of best interest of child values preferences of family.; For difficult life-prolonging decisions or clarification of treatment options, consider further consultation w/independent clinical teams.
Supportive Treatment of Individuals with Acute Infantile GM2 Activator Deficiency Manifestation/Concern	Treatment	Considerations/Other
Seizures	Standardized treatment w/ASM by experienced neurologist/epileptologist	Seizures are often progressive refractory.; Many ASMs may be effective; none has been demonstrated effective specifically for this disorder.; Complete seizure control is seldom achieved requires balancing w/sedative side effects of ASMs.; Education of parents/caregivers1 Abnormal tone/
Impaired mobility	PT/OT	For prevention of contractures
Feeding difficulties	Gastrostomy tube	Will longevity but not preserve developmental function
Bowel dysfunction	Monitor for constipation.	Stool softeners, prokinetics, osmotic agents, or laxatives as needed Aspiration risks/
Excess secretion	Gastrostomy tube, vibrator vest, improved pulmonary toilet, suppression of saliva production	Will aspiration improve longevity but not preserve developmental function
Family support	In-home nursing respite care	Support for health quality of life of caregivers sibs Ethics
consultation	Clinical ethics services	Assess health care decisions in context of best interest of child values preferences of family.; For difficult life-prolonging decisions or clarification of treatment options, consider further consultation w/independent clinical teams.

Source: GeneReviews — "GM2 Activator Deficiency"

Research Type	Count	% of Total
Laboratory research	15	30%
Patient case studies	9	18%
New treatment approaches	9	18%
Testing and diagnosis research	5	10%
Disease patterns and progression	5	10%
Clinical study results	3	6%
Other research	2	4%
Research summaries	2	4%

Kisho

GM2 gangliosidosis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Impaired mobility

Nutrition/feeding

Respiratory

Recent Publications

GM2 gangliosidosis

Overview

Clinical Presentation

Clinical Guidance

Diagnosis

Diagnostic Criteria

Suggestive Findings

Treatment

Orphan Drug Designations

Prognosis

Surveillance Guidelines

Research Landscape

Medical References

External Resources

Orphanet

GARD

Subtypes

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Differential Diagnosis

Management Guidelines

Clinical Guidance

Therapies Under Investigation

Clinical Trials

Impaired mobility

Nutrition/feeding

Respiratory

Recent Publications