Sandhoff disease

Summary

Sandhoff disease (MONDO:0010006) is a disease caused by HEXB (GenCC Definitive), with 3 cohort genes and 16 clinical trials. Top therapeutic interventions include miglustat, busulfan, and cyclophosphamide anhydrous.

At a glance

• Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
• Causal gene: HEXB (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 828
• Phenotypes (HPO): 19
• Clinical trials: 16

Clinical features

Epidemiology

Prevalence records

9 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 1 000 000	0.67	Europe	Validated
Prevalence at birth	1-9 / 100 000	1.49	Portugal	Validated
Prevalence at birth	1-9 / 1 000 000	0.34	Netherlands	Validated
Prevalence at birth	1-9 / 1 000 000	0.19	Czech Republic	Validated
Prevalence at birth	1-9 / 1 000 000	0.26	Australia	Validated
Prevalence at birth	1-9 / 1 000 000	0.95	Turkey	Validated
Prevalence at birth	1-9 / 1 000 000	0.3	United States	Validated
Prevalence at birth	1-9 / 1 000 000	0.38	Sweden	Validated
Point prevalence	1-9 / 1 000 000		Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

19 HPO clinical features (Orphanet curated; top 19 by frequency):

HPO ID	Term	Frequency
HP:0000256	Macrocephaly	Very frequent (80-99%)
HP:0000365	Hearing impairment	Very frequent (80-99%)
HP:0000618	Blindness	Very frequent (80-99%)
HP:0001250	Seizure	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001508	Failure to thrive	Very frequent (80-99%)
HP:0002333	Motor deterioration	Very frequent (80-99%)
HP:0002808	Kyphosis	Very frequent (80-99%)
HP:0004343	Abnormal glycosphingolipid metabolism	Very frequent (80-99%)
HP:0007272	Progressive psychomotor deterioration	Very frequent (80-99%)
HP:0010729	Cherry red spot of the macula	Very frequent (80-99%)
HP:0100022	Abnormality of movement	Very frequent (80-99%)
HP:0000293	Full cheeks	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001744	Splenomegaly	Frequent (30-79%)
HP:0002205	Recurrent respiratory infections	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0001635	Congestive heart failure	Occasional (5-29%)
HP:0002652	Skeletal dysplasia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Sandhoff disease
Mondo ID	MONDO:0010006
MeSH	D012497
OMIM	268800
Orphanet	796
DOID	DOID:3323
ICD-10-CM	E75.01
ICD-11	708581915
NCIT	C85052
SNOMED CT	23849003
UMLS	C0036161
MedGen	11313
GARD	0002521
NORD	1688
Is cancer (heuristic)	no

Also known as: GM2 gangliosidosis 0 variant · GM2 gangliosidosis, 0 variant · Hexosaminidases A and B deficiency · Sandhoff disease · Sandhoff Jatzkewitz disease

Data availability: 828 ClinVar variants · 6 GenCC gene-disease records · 14 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › Sandhoff disease

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, neuroocular syndrome, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Subtypes (3): Sandhoff disease, infantile form, Sandhoff disease, juvenile form, Sandhoff disease, adult form

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

345 likely benign, 91 uncertain significance, 67 pathogenic, 42 likely pathogenic, 21 pathogenic/likely pathogenic, 16 conflicting classifications of pathogenicity, 14 benign, 3 benign/likely benign, 1 likely benign; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
2423202	NC_000005.9:g.(?73980960)(74041702_?)del	GFM2	Pathogenic	criteria provided, single submitter
1012509	NM_000521.4(HEXB):c.876del (p.His294fs)	HEXB	Pathogenic	criteria provided, multiple submitters, no conflicts
1012510	NM_000521.4(HEXB):c.1165dup (p.Gln389fs)	HEXB	Pathogenic	criteria provided, multiple submitters, no conflicts
1067213	NM_000521.4(HEXB):c.1563_1573del (p.Met522fs)	HEXB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069640	NM_000521.4(HEXB):c.1144A>T (p.Lys382Ter)	HEXB	Pathogenic	criteria provided, single submitter
1070002	NM_000521.4(HEXB):c.1156_1159del (p.Phe386fs)	HEXB	Pathogenic	criteria provided, single submitter
1070441	NM_000521.4(HEXB):c.1017_1018del (p.Glu339fs)	HEXB	Pathogenic	criteria provided, single submitter
1070612	NC_000005.9:g.(?73981066)(74017020_?)del	HEXB	Pathogenic	criteria provided, single submitter
1070645	NM_000521.4(HEXB):c.782_785del (p.Ser261fs)	HEXB	Pathogenic	criteria provided, multiple submitters, no conflicts
1071217	NM_000521.4(HEXB):c.1578T>G (p.Tyr526Ter)	HEXB	Pathogenic	criteria provided, single submitter
1073343	NM_000521.4(HEXB):c.1299_1303del (p.Arg435fs)	HEXB	Pathogenic	criteria provided, single submitter
1074051	NM_000521.4(HEXB):c.1389_1393del (p.Tyr463_Lys465delinsTer)	HEXB	Pathogenic	criteria provided, single submitter
1074772	NM_000521.4(HEXB):c.1586_1589del (p.Leu529fs)	HEXB	Pathogenic	criteria provided, single submitter
1301333	NM_000521.4(HEXB):c.1598G>A (p.Arg533His)	HEXB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1375497	NM_000521.4(HEXB):c.452T>A (p.Leu151Ter)	HEXB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1379520	NM_000521.4(HEXB):c.1264dup (p.Glu422fs)	HEXB	Pathogenic	criteria provided, single submitter
1398058	NM_000521.4(HEXB):c.916_917del (p.Leu306fs)	HEXB	Pathogenic	criteria provided, single submitter
1405131	NC_000005.9:g.(?74011325)(74017010_?)del	HEXB	Pathogenic	criteria provided, single submitter
1415401	NM_000521.4(HEXB):c.1278_1279del (p.Asp426fs)	HEXB	Pathogenic	criteria provided, single submitter
1423387	NM_000521.4(HEXB):c.926G>A (p.Cys309Tyr)	HEXB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1442270	NM_000521.4(HEXB):c.731del (p.Phe244fs)	HEXB	Pathogenic	criteria provided, single submitter
1450108	NM_000521.4(HEXB):c.1159_1160insTTTTTTTTTTTTTTTTTTTNNNNNNNNNNTTTTTCTTTTCCTTTTATTTTATTTTTTGAGACGGAGTCTTGCTCTGTTGTCTGGGTGGAGTGCAGTGGTGCAATCTCGGCTCACTGCAACCTCTTCCTCCCAGGTTGAAGCGGAAACTAGAATCTTTCT (p.Tyr387delinsPhePhePhePhePhePheXaaXaaXaaXaaPhePhePheSerPheTyrPheIlePheTer)	HEXB	Pathogenic	criteria provided, single submitter
1454030	NM_000521.4(HEXB):c.1024del (p.Glu342fs)	HEXB	Pathogenic	criteria provided, single submitter
1455054	NC_000005.9:g.(?73985143)(74014806_?)del	HEXB	Pathogenic	criteria provided, single submitter
1458169	NM_000521.4(HEXB):c.1404del (p.Asp470fs)	HEXB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458290	NM_000521.4(HEXB):c.1303_1304insT (p.Arg435fs)	HEXB	Pathogenic	criteria provided, single submitter
1459374	NM_000521.4(HEXB):c.992_993insAGTATGTA (p.Ser331fs)	HEXB	Pathogenic	criteria provided, single submitter
1704505	NC_000005.9:g.(?73980968)(73992932_74001043)del	HEXB	Pathogenic	criteria provided, single submitter
1726024	NM_000521.4(HEXB):c.341_342del (p.Glu114fs)	HEXB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1726081	NM_000521.4(HEXB):c.1434dup (p.Gln479fs)	HEXB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
HEXB	Definitive	Autosomal recessive	Sandhoff disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HEXB	Orphanet:309155	Sandhoff disease, infantile form
HEXB	Orphanet:309162	Sandhoff disease, juvenile form
HEXB	Orphanet:309169	Sandhoff disease, adult form
GFM2	Orphanet:565624	Combined oxidative phosphorylation defect type 39

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
HEXB	HGNC:4879	ENSG00000049860	P07686	Beta-hexosaminidase subunit beta	gencc,clinvar
GFM2	HGNC:29682	ENSG00000164347	Q969S9	Ribosome-releasing factor 2, mitochondrial	clinvar
ANKDD1B	HGNC:32525	ENSG00000189045	A6NHY2	Ankyrin repeat and death domain-containing protein 1B	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HEXB	Beta-hexosaminidase subunit beta	Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides.
GFM2	Ribosome-releasing factor 2, mitochondrial	Mitochondrial GTPase that mediates the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	5.8×	0.345
Enzyme (other)	1	4.0×	0.345
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HEXB	Enzyme (other)	yes	3.2.1.52	GH20_cat, GH_hydrolase_sf, GH20
GFM2	Other/Unknown	no		EFG_V-like, T_Tr_GTP-bd_dom, Small_GTP-bd
ANKDD1B	Scaffold/PPI	no		Death_dom, Ankyrin_rpt, DEATH-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
placenta	1
stromal cell of endometrium	1
bronchial epithelial cell	1
left ventricle myocardium	1
tibialis anterior	1
male germ line stem cell (sensu Vertebrata) in testis	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HEXB	289	ubiquitous	marker	placenta, stromal cell of endometrium, calcaneal tendon
GFM2	262	ubiquitous	marker	left ventricle myocardium, tibialis anterior, bronchial epithelial cell
ANKDD1B	132		marker	right uterine tube, male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HEXB	2,557
GFM2	1,997
ANKDD1B	1,056

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HEXB	P07686	8
GFM2	Q969S9	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANKDD1B	A6NHY2	83.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective HEXB causes GM2G2 (Hyaluronan metabolism)	1	5710.0×	0.002	HEXB
Keratan sulfate degradation	1	356.9×	0.009	HEXB
Hyaluronan degradation	1	356.9×	0.009	HEXB
CS/DS degradation	1	271.9×	0.009	HEXB
Glycosphingolipid catabolism	1	146.4×	0.014	HEXB
Mitochondrial translation	1	68.8×	0.024	GFM2
Mitochondrial translation termination	1	54.9×	0.026	GFM2
Translation	1	31.0×	0.040	GFM2
Neutrophil degranulation	1	11.5×	0.094	HEXB
Metabolism of proteins	1	6.2×	0.155	GFM2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
male courtship behavior	1	5617.3×	0.005	HEXB
dermatan sulfate proteoglycan catabolic process	1	1404.3×	0.006	HEXB
mitochondrial translational termination	1	1123.5×	0.006	GFM2
chondroitin sulfate proteoglycan catabolic process	1	936.2×	0.006	HEXB
glycosaminoglycan metabolic process	1	802.5×	0.006	HEXB
astrocyte cell migration	1	802.5×	0.006	HEXB
ganglioside catabolic process	1	624.1×	0.006	HEXB
penetration of zona pellucida	1	510.7×	0.006	HEXB
oligosaccharide catabolic process	1	510.7×	0.006	HEXB
N-acetylglucosamine metabolic process	1	401.2×	0.007	HEXB
hyaluronan catabolic process	1	330.4×	0.007	HEXB
ribosome disassembly	1	330.4×	0.007	GFM2
N-glycan processing	1	244.2×	0.009	HEXB
phospholipid biosynthetic process	1	224.7×	0.009	HEXB
lipid storage	1	181.2×	0.011	HEXB
neuron cellular homeostasis	1	151.8×	0.012	HEXB
oogenesis	1	127.7×	0.013	HEXB
neuromuscular process controlling balance	1	110.1×	0.015	HEXB
lysosome organization	1	102.1×	0.015	HEXB
myelination	1	83.8×	0.017	HEXB
single fertilization	1	61.1×	0.022	HEXB
locomotory behavior	1	59.8×	0.022	HEXB
mitochondrial translation	1	57.9×	0.022	GFM2
intracellular calcium ion homeostasis	1	48.4×	0.025	HEXB
skeletal system development	1	41.9×	0.027	HEXB
regulation of cell shape	1	41.0×	0.027	HEXB
sensory perception of sound	1	33.6×	0.032	HEXB
signal transduction	1	5.3×	0.182	ANKDD1B
positive regulation of transcription by RNA polymerase II	1	5.0×	0.188	HEXB

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Miglustat	Phase 3 (in late-stage trials)
Venglustat	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Busulfan, Trenonacog Alfa.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
HEXB	PYRIMETHAMINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HEXB	1	4
GFM2	0	0
ANKDD1B	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRIMETHAMINE	4	HEXB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
HEXB	53	Binding:53

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HEXB	3.2.1.52	beta-N-acetylhexosaminidase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	HEXB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	GFM2, ANKDD1B

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GFM2	0	—
ANKDD1B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 16.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	7
PHASE3	2
PHASE1/PHASE2	2
PHASE1	2
PHASE4	1
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02030015	PHASE4	TERMINATED	Synergistic Enteral Regimen for Treatment of the Gangliosidoses
NCT00176904	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant for Inborn Errors of Metabolism
NCT00672022	PHASE3	COMPLETED	Pharmacokinetics, Safety and Tolerability of Zavesca (Miglustat) in Patients With Infantile Onset Gangliosidosis: Single and Steady State Oral Doses
NCT04221451	PHASE3	TERMINATED	A Multinational, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Pharmacodynamics, Pharmacokinetics, and Safety of Venglustat in Late-onset GM2
NCT01102686	PHASE1/PHASE2	COMPLETED	Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)
NCT01372228	PHASE1/PHASE2	TERMINATED	Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders
NCT03759665	PHASE2	COMPLETED	N-Acetyl-L-Leucine for GM2 Gangliosidosis (Tay-Sachs and Sandhoff Disease)
NCT02254863	PHASE1	RECRUITING	UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
NCT04669535	PHASE1	TERMINATED	A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease
NCT00668187	Not specified	RECRUITING	A Natural History Study of the Gangliosidoses
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT06614569	Not specified	ACTIVE_NOT_RECRUITING	Long-Term Follow-Up of Subjects Treated With AXO-AAV-GM2 for Tay-Sachs or Sandhoff Disease
NCT01869270	Not specified	COMPLETED	Gene Therapy for Tay-Sachs Disease
NCT04470713	Not specified	COMPLETED	Natural History Study for Pediatric Patients With Early Onset of Either GM1 Gangliosidosis, GM2 Gangliosidoses, or Gaucher Disease Type 2
NCT04624789	Not specified	UNKNOWN	Registry Gangliosidoses
NCT05109793	Not specified	COMPLETED	GM1 and GM2 Gangliosidosis PROspective Neurological Disease TrajectOry Study (PRONTO)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MIGLUSTAT	4	2
BUSULFAN	4	1
CYCLOPHOSPHAMIDE ANHYDROUS	4	1
LEVACETYLLEUCINE	4	1
PYRIMETHAMINE	4	1
TRENONACOG ALFA	3	1
VENGLUSTAT	3	1
GILAVEBEXAGENE ANVUPARVOVEC	1	1