Glycogen storage disease due to acid maltase deficiency, late-onset

Summary

Glycogen storage disease due to acid maltase deficiency, late-onset (MONDO:0018485) is a disease with 1 cohort gene and 3 clinical trials. Top therapeutic interventions include vanglusagene ensiparvovec.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 15
• Clinical trials: 3

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Prevalence at birth	1-9 / 100 000	1.75	Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	glycogen storage disease due to acid maltase deficiency, late-onset
Mondo ID	MONDO:0018485
OMIM	621314
Orphanet	420429
SNOMED CT	722343009
UMLS	C0342753
MedGen	575206
GARD	0021746
Is cancer (heuristic)	no

Also known as: Alpha-1,4-glucosidase acid deficiency, late onset · Alpha-1,4-glucosidase acid deficiency, late-onset · glycogen storage disease type 2, late onset · glycogen storage disease type 2, late-onset · glycogen storage disease type II, late onset · glycogen storage disease type II, late-onset · glycogenosis type 2, late onset · glycogenosis type 2, late-onset · glycogenosis type II, late onset · glycogenosis type II, late-onset · GSD due to acid maltase deficiency, late onset · GSD due to acid maltase deficiency, late-onset · GSD type 2, late onset · GSD type 2, late-onset · GSD type II, late onset · GSD type II, late-onset · LOPD · Pompe disease, late onset · Pompe disease, late-onset

Data availability: 15 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn carbohydrate metabolic disorder › disorder of glycogen metabolism › glycogen storage disease II › glycogen storage disease due to acid maltase deficiency, late-onset

Related subtypes (1): glycogen storage disease due to acid maltase deficiency, infantile onset

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

15 retrieved; paginated sample, class counts are floors:

10 pathogenic, 2 uncertain significance, 2 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4023	NM_000152.5(GAA):c.1927G>A (p.Gly643Arg)	GAA	Pathogenic	reviewed by expert panel
4024	NM_000152.5(GAA):c.2173C>T (p.Arg725Trp)	GAA	Pathogenic	reviewed by expert panel
4027	NM_000152.5(GAA):c.-32-13T>G	GAA	Pathogenic	reviewed by expert panel
4031	NM_000152.5(GAA):c.2483_2646+1del	GAA	Pathogenic	no assertion criteria provided
4032	NM_000152.5(GAA):c.1634C>T (p.Pro545Leu)	GAA	Pathogenic	criteria provided, multiple submitters, no conflicts
4033	NM_000152.5(GAA):c.525del (p.Glu176fs)	GAA	Pathogenic	reviewed by expert panel
4034	NM_000152.5(GAA):c.2560C>T (p.Arg854Ter)	GAA	Pathogenic	reviewed by expert panel
4036	NM_000152.5(GAA):c.877G>A (p.Gly293Arg)	GAA	Pathogenic	reviewed by expert panel
551193	NM_000152.5(GAA):c.1076-1G>A	GAA	Pathogenic/Likely pathogenic	no assertion criteria provided
810666	NM_000152.5(GAA):c.2074C>T (p.Gln692Ter)	GAA	Pathogenic	criteria provided, single submitter
810667	NM_000152.5(GAA):c.1910_1918del (p.Leu637_Val639del)	GAA	Pathogenic	no assertion criteria provided
289367	NM_000152.5(GAA):c.1082C>G (p.Pro361Arg)	GAA	Likely pathogenic	reviewed by expert panel
4026	NM_000152.5(GAA):c.1585_1586delinsGT (p.Ser529Val)	GAA	Likely pathogenic	reviewed by expert panel
1176696	NM_000152.5(GAA):c.1069G>A (p.Val357Ile)	GAA	Uncertain significance	criteria provided, multiple submitters, no conflicts
4035	NM_000152.5(GAA):c.710C>T (p.Ala237Val)	GAA	Uncertain significance	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 2 · 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
GAA	Definitive	Autosomal recessive	glycogen storage disease II	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GAA	Orphanet:308552	Glycogen storage disease due to acid maltase deficiency, infantile onset
GAA	Orphanet:420429	Glycogen storage disease due to acid maltase deficiency, late-onset

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GAA	HGNC:4065	ENSG00000171298	P10253	Lysosomal alpha-glucosidase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GAA	Lysosomal alpha-glucosidase	Essential for the degradation of glycogen in lysosomes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GAA	Enzyme (other)	yes	3.2.1.20	Glyco_hydro_31_TIM, P_trefoil_dom, Gal_mutarotase_sf_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
left testis	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GAA	261	ubiquitous	marker	granulocyte, left testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GAA	2,116

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GAA	P10253	19

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glycogen storage diseases	1	5710.0×	0.001	GAA
Glycogen storage disease type II (GAA)	1	5710.0×	0.001	GAA
Glycogen metabolism	1	1903.3×	0.002	GAA
Diseases of carbohydrate metabolism	1	815.7×	0.003	GAA
Glycogen breakdown (glycogenolysis)	1	761.3×	0.003	GAA
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.017	GAA
Diseases of metabolism	1	80.4×	0.021	GAA
Innate Immune System	1	25.5×	0.058	GAA
Neutrophil degranulation	1	23.1×	0.058	GAA
Disease	1	13.1×	0.084	GAA
Immune System	1	13.0×	0.084	GAA
Metabolism	1	11.6×	0.086	GAA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
maltose metabolic process	1	16852.0×	3e-04	GAA
sucrose metabolic process	1	16852.0×	3e-04	GAA
obsolete vacuolar sequestering	1	16852.0×	3e-04	GAA
diaphragm contraction	1	4213.0×	0.001	GAA
tissue development	1	1872.4×	0.002	GAA
glycophagy	1	1404.3×	0.002	GAA
glycogen catabolic process	1	1203.7×	0.002	GAA
neuromuscular process controlling posture	1	1053.2×	0.002	GAA
regulation of the force of heart contraction	1	991.3×	0.002	GAA
muscle cell cellular homeostasis	1	648.1×	0.003	GAA
aorta development	1	561.7×	0.003	GAA
cardiac muscle contraction	1	401.2×	0.003	GAA
heart morphogenesis	1	374.5×	0.003	GAA
neuromuscular process controlling balance	1	330.4×	0.004	GAA
lysosome organization	1	306.4×	0.004	GAA
glucose metabolic process	1	255.3×	0.004	GAA
locomotory behavior	1	179.3×	0.006	GAA

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
GAA	DIENESTROL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GAA	112	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIENESTROL	4	GAA
MIGLUSTAT	4	GAA
DICLOFENAC SODIUM	4	GAA
DIBUCAINE	4	GAA
AMLEXANOX	4	GAA
MIGALASTAT	4	GAA
ARIPIPRAZOLE	4	GAA
DULOXETINE	4	GAA
LABETALOL HYDROCHLORIDE	4	GAA
MORICIZINE HYDROCHLORIDE	4	GAA
PHENYLEPHRINE HYDROCHLORIDE	4	GAA
DEMECLOCYCLINE HYDROCHLORIDE	4	GAA
DOXAZOSIN MESYLATE	4	GAA
PRILOCAINE HYDROCHLORIDE	4	GAA
FLUOROMETHOLONE	4	GAA
PHENELZINE SULFATE	4	GAA
RABEPRAZOLE SODIUM	4	GAA
METHYSERGIDE MALEATE	4	GAA
ACRISORCIN	4	GAA
ECONAZOLE NITRATE	4	GAA
ISOETHARINE MESYLATE	4	GAA
QUINESTROL	4	GAA
DEFEROXAMINE MESYLATE	4	GAA
MAPROTILINE HYDROCHLORIDE	4	GAA
EPINEPHRINE BITARTRATE	4	GAA
PROCHLORPERAZINE MALEATE	4	GAA
IRBESARTAN	4	GAA
OXYTETRACYCLINE	4	GAA
DOPAMINE HYDROCHLORIDE	4	GAA
PRAZOSIN HYDROCHLORIDE	4	GAA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
GAA	280	Binding:267, Functional:13

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GAA	3.2.1.20	alpha-glucosidase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
GAA	280

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
DIENESTROL	4	GAA
MIGLUSTAT	4	GAA
DICLOFENAC SODIUM	4	GAA
DIBUCAINE	4	GAA
AMLEXANOX	4	GAA
MIGALASTAT	4	GAA
ARIPIPRAZOLE	4	GAA
DULOXETINE	4	GAA
LABETALOL HYDROCHLORIDE	4	GAA
MORICIZINE HYDROCHLORIDE	4	GAA
PHENYLEPHRINE HYDROCHLORIDE	4	GAA
DEMECLOCYCLINE HYDROCHLORIDE	4	GAA
DOXAZOSIN MESYLATE	4	GAA
PRILOCAINE HYDROCHLORIDE	4	GAA
FLUOROMETHOLONE	4	GAA
PHENELZINE SULFATE	4	GAA
RABEPRAZOLE SODIUM	4	GAA
METHYSERGIDE MALEATE	4	GAA
ACRISORCIN	4	GAA
ECONAZOLE NITRATE	4	GAA
ISOETHARINE MESYLATE	4	GAA
QUINESTROL	4	GAA
DEFEROXAMINE MESYLATE	4	GAA
MAPROTILINE HYDROCHLORIDE	4	GAA
EPINEPHRINE BITARTRATE	4	GAA
PROCHLORPERAZINE MALEATE	4	GAA
IRBESARTAN	4	GAA
OXYTETRACYCLINE	4	GAA
DOPAMINE HYDROCHLORIDE	4	GAA
PRAZOSIN HYDROCHLORIDE	4	GAA

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GAA
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	2
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04093349	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
NCT07282847	PHASE1/PHASE2	RECRUITING	A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late Onset Pompe Disease (PROGRESS-GT LOPD)
NCT03893240	Not specified	COMPLETED	Neutralizing Antibody Seroprevalence Study With a Retrospective Component in Participants With Late-Onset Pompe Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
VANGLUSAGENE ENSIPARVOVEC	1	1