Adult polyglucosan body disease

Summary

Adult polyglucosan body disease (MONDO:0009897) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include triheptanoin.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 124
• Phenotypes (HPO): 18
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

18 HPO clinical features (Orphanet curated; top 18 by frequency):

HPO ID	Term	Frequency
HP:0000011	Neurogenic bladder	Very frequent (80-99%)
HP:0000020	Urinary incontinence	Very frequent (80-99%)
HP:0001249	Intellectual disability	Very frequent (80-99%)
HP:0001257	Spasticity	Very frequent (80-99%)
HP:0001269	Hemiparesis	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0001324	Muscle weakness	Very frequent (80-99%)
HP:0002839	Urinary bladder sphincter dysfunction	Very frequent (80-99%)
HP:0007256	Abnormal pyramidal sign	Very frequent (80-99%)
HP:0009830	Peripheral neuropathy	Very frequent (80-99%)
HP:0000708	Atypical behavior	Frequent (30-79%)
HP:0002936	Distal sensory impairment	Frequent (30-79%)
HP:0200042	Skin ulcer	Frequent (30-79%)
HP:0000726	Dementia	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001376	Limitation of joint mobility	Occasional (5-29%)
HP:0002071	Abnormality of extrapyramidal motor function	Occasional (5-29%)
HP:0003457	EMG abnormality	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	adult polyglucosan body disease
Mondo ID	MONDO:0009897
MeSH	C564878
OMIM	263570
Orphanet	206583
SNOMED CT	721099001
UMLS	C1849722
MedGen	342338
GARD	0000108
NORD	1591
Is cancer (heuristic)	no

Also known as: APBD · APBN · polyglucosan body disease, adult · polyglucosan body neuropathy, adult form

Data availability: 124 ClinVar variants · 2 GenCC gene-disease records.

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 due to glycogen branching enzyme deficiency › adult polyglucosan body disease

Related subtypes (7): glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form, glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form, glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form, glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form, glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form, glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form, glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular 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

124 retrieved; paginated sample, class counts are floors:

35 uncertain significance, 29 conflicting classifications of pathogenicity, 17 pathogenic/likely pathogenic, 13 benign, 12 benign/likely benign, 12 likely pathogenic, 4 pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1053439	NM_000158.4(GBE1):c.2081T>A (p.Ile694Asn)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1341385	NM_000158.4(GBE1):c.1825G>T (p.Glu609Ter)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1341394	NM_000158.4(GBE1):c.895G>T (p.Gly299Ter)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1426965	NM_000158.4(GBE1):c.466_470del (p.Arg156fs)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454134	NM_000158.4(GBE1):c.321G>A (p.Trp107Ter)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
180651	NM_000158.4(GBE1):c.1544G>A (p.Arg515His)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1952542	NM_000158.4(GBE1):c.556-1G>A	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
208584	NM_000158.4(GBE1):c.691+2T>C	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2152486	NM_000158.4(GBE1):c.167del (p.Ile55_Leu56insTer)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225145	NM_000158.4(GBE1):c.2053-3358_2053-3350delinsTGTTTTTTACATGACAGGT	GBE1	Pathogenic	criteria provided, multiple submitters, no conflicts
2777	NM_000158.4(GBE1):c.986A>C (p.Tyr329Ser)	GBE1	Pathogenic	criteria provided, multiple submitters, no conflicts
2778	NM_000158.4(GBE1):c.671T>C (p.Leu224Pro)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2781	NM_000158.4(GBE1):c.1570C>T (p.Arg524Ter)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2788	NM_000158.4(GBE1):c.1883A>G (p.His628Arg)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2790	NM_000158.4(GBE1):c.708G>C (p.Gln236His)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2791	NM_000158.4(GBE1):c.784C>T (p.Arg262Cys)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2929113	NM_000158.4(GBE1):c.1680C>G (p.Tyr560Ter)	GBE1	Pathogenic	criteria provided, multiple submitters, no conflicts
346787	NM_000158.4(GBE1):c.1604A>G (p.Tyr535Cys)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371491	NM_000158.4(GBE1):c.288del (p.Gly97fs)	GBE1	Pathogenic	criteria provided, multiple submitters, no conflicts
435291	NM_000158.4(GBE1):c.415G>T (p.Gly139Ter)	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
639425	NM_000158.4(GBE1):c.1803+2T>C	GBE1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1516218	NM_000158.4(GBE1):c.2052+1G>T	GBE1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1952687	NM_000158.4(GBE1):c.993-2A>G	GBE1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675857	NM_000158.4(GBE1):c.854T>G (p.Leu285Ter)	GBE1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3233938	NM_000158.4(GBE1):c.1666A>T (p.Asn556Tyr)	GBE1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3589640	NM_000158.4(GBE1):c.1782T>A (p.Tyr594Ter)	GBE1	Likely pathogenic	criteria provided, single submitter
3589641	NM_000158.4(GBE1):c.1771G>T (p.Glu591Ter)	GBE1	Likely pathogenic	criteria provided, single submitter
3589643	NM_000158.4(GBE1):c.1244C>G (p.Ser415Ter)	GBE1	Likely pathogenic	criteria provided, single submitter
3589644	NM_000158.4(GBE1):c.995G>A (p.Trp332Ter)	GBE1	Likely pathogenic	criteria provided, single submitter
3589645	NM_000158.4(GBE1):c.933dup (p.His312fs)	GBE1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 8 · 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
GBE1	Moderate	Autosomal recessive	adult polyglucosan body disease	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GBE1	Orphanet:206583	Adult polyglucosan body disease
GBE1	Orphanet:308621	Glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form
GBE1	Orphanet:308638	Glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form
GBE1	Orphanet:308655	Glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form
GBE1	Orphanet:308670	Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form
GBE1	Orphanet:308684	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form
GBE1	Orphanet:308698	Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form
GBE1	Orphanet:308712	Glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form

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
GBE1	HGNC:4180	ENSG00000114480	Q04446	1,4-alpha-glucan-branching enzyme	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GBE1	1,4-alpha-glucan-branching enzyme	Glycogen-branching enzyme participates in the glycogen biosynthetic process along with glycogenin and glycogen synthase.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GBE1	Antibody/Immunoglobulin	yes		Glyco_hydro_13_N, GH13_cat_dom, A-amylase/branching_C

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
biceps brachii	1
gluteal muscle	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GBE1	293	ubiquitous	marker	gluteal muscle, tibialis anterior, biceps brachii

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GBE1	3,402

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GBE1	Q04446	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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 disease type IV (GBE1)	1	3806.7×	5e-04	GBE1
Glycogen synthesis	1	815.7×	0.001	GBE1

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
glycogen biosynthetic process	1	936.2×	0.004	GBE1
glycogen metabolic process	1	526.6×	0.004	GBE1
generation of precursor metabolites and energy	1	343.9×	0.004	GBE1
negative regulation of neuron apoptotic process	1	110.9×	0.009	GBE1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GBE1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	GBE1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GBE1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00947960	PHASE2	COMPLETED	Triheptanoin Treatment Trial for Patients With Adult Polyglucosan Body Disease
NCT02683512	Not specified	RECRUITING	GBE Deficiency (GSD IV and APBD) Natural History Study

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TRIHEPTANOIN	4	1