👪

Inheritance

1

Autosomal recessive inheritance HP:0000007

Adult polyglucosan body disease is inherited in an autosomal recessive manner due to biallelic pathogenic variants in GBE1.

Autosomal recessive inheritance

Show evidence (2 references)

ORPHA:206583 SUPPORT Other

"- Autosomal recessive"

Orphanet lists autosomal recessive inheritance for APBD.

PMID:33141444 SUPPORT Human Clinical

"Adult polyglucosan body disease (APBD) represents a complex autosomal recessive inherited neurometabolic disorder due to homozygous or compound heterozygous pathogenic variants in GBE1 gene"

This review directly states autosomal recessive inheritance and biallelic GBE1 variants.

⚙

Pathophysiology

5

GBE1 deficiency and impaired glycogen branching

Pathogenic GBE1 variants reduce glycogen branching enzyme activity, impairing glycogen synthesis and producing poorly branched glycogen.

GBE1 link

glycogen biosynthetic process link ↓ DECREASED glycogen metabolic process link ⚠ ABNORMAL

1,4-alpha-glucan branching enzyme activity link ↓ DECREASED

Downstream

Polyglucosan body accumulation Impaired glycogen branching leads to accumulation of poorly branched glycogen known as polyglucosan.

Reduced glycogen branching enzyme activity Pathogenic GBE1 variants reduce or abolish glycogen branching enzyme activity.

Show evidence (2 references)

PMID:36796138 SUPPORT Human Clinical

"Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity."

This directly supports GBE1 variants causing reduced glycogen branching enzyme activity.

PMID:25665141 SUPPORT Human Clinical

"We identified a deep intronic mutation in this allele, GBE1-IVS15+5289_5297delGTGTGGTGGinsTGTTTTTTACATGACAGGT, which acts as a gene trap, creating an ectopic last exon."

This supports pathogenic GBE1 variants as molecular causes of APBD.

Polyglucosan body accumulation

Deficient glycogen branching enzyme activity causes storage of abnormal glycogen as polyglucosan bodies in central nervous system, peripheral nerve, autonomic fibers, and skeletal muscle tissues.

glycogen metabolic process link ⚠ ABNORMAL

Downstream

Neurogenic bladder Autonomic fiber and nervous system involvement contributes to bladder dysfunction.

Peripheral neuropathy Peripheral nerve involvement produces axonal neuropathy and distal sensory impairment.

Peripheral nerve, autonomic, and neuromuscular involvement Polyglucosan storage involves peripheral nerve, autonomic fibers, and skeletal muscle, providing a shared branch for bladder, neuropathic, sensory, EMG, weakness, and mobility-complication phenotypes.

Spasticity Central motor tract involvement contributes to spastic gait and pyramidal signs.

White matter and motor tract degeneration Polyglucosan storage involves brain white matter, spinal cord, and brainstem motor pathways, connecting storage pathology to white matter and motor tract degeneration.

Proteostasis and cellular stress dysregulation APBD polyglucosan storage and GBE1 deficiency are associated with secondary cellular stress and proteostasis pathway dysregulation in patient-derived lymphoblasts.

Show evidence (2 references)

PMID:33141444 SUPPORT Human Clinical

"deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies, involving the skeletal muscle, diaphragm, peripheral nerve (including autonomic fibers), brain white matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser extent heart,..."

This directly supports the affected tissues and polyglucosan storage mechanism.

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"Polyglucosan bodies accumulate in the central and peripheral nervous systems and are often associated with glycogen branching enzyme (GBE) deficiency."

This links GBE deficiency to polyglucosan body accumulation in central and peripheral nervous systems.

Peripheral nerve, autonomic, and neuromuscular involvement

APBD storage pathology affects peripheral nerves, autonomic fibers, nerve roots, and skeletal muscle, producing bladder sphincter dysfunction, neuropathy with distal sensory impairment, weakness, EMG abnormalities, and secondary mobility or skin complications.

transmission of nerve impulse link ⚠ ABNORMAL

Downstream

Neurogenic bladder Autonomic involvement produces neurogenic bladder.

Urinary incontinence Neurogenic bladder and autonomic dysfunction lead to urinary incontinence.

Urinary bladder sphincter dysfunction Autonomic and bladder pathway involvement produces bladder sphincter dysfunction.

Orthostatic hypotension Autonomic dysfunction in classic GBE1-APBD can include orthostatic hypotension.

Constipation Autonomic dysfunction in classic GBE1-APBD can include constipation.

Peripheral neuropathy Peripheral nerve storage pathology produces axonal neuropathy.

Distal sensory impairment Axonal neuropathy with vibration loss produces distal sensory impairment.

Muscle weakness Skeletal muscle and neuromuscular involvement can manifest as weakness.

EMG abnormality Neuromuscular involvement can produce abnormal electromyography.

Limitation of joint mobility Reduced mobility and neuromuscular disease may contribute to joint mobility limitation.

Skin ulcer Skin ulcers are modeled as a secondary complication of neuropathy or reduced mobility.

Show evidence (3 references)

PMID:33141444 SUPPORT Human Clinical

"deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies, involving the skeletal muscle, diaphragm, peripheral nerve (including autonomic fibers), brain white matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser extent heart,..."

Clinical review supports the affected peripheral, autonomic, and neuromuscular tissues.

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%)."

Natural history cohort supports autonomic bladder involvement, vibration loss, and axonal neuropathy.

PMID:20301758 SUPPORT Other

"neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, autonomic dysfunction"

GeneReviews summarizes the same bladder, motor, sensory, and autonomic involvement in classic GBE1-APBD.

White matter and motor tract degeneration

APBD neuroimaging shows white matter abnormalities and medulla/spinal atrophy involving motor tracts, consistent with progressive spastic gait and pyramidal signs.

Downstream

Gait disturbance

Abnormal pyramidal sign

Dementia

Ataxia Cerebellar and brainstem involvement can produce ataxia.

Atypical behavior White matter and cognitive involvement can be accompanied by behavioral changes.

Intellectual disability APBD cognitive involvement is linked conservatively to the Orphanet intellectual disability phenotype.

Hemiparesis Motor tract degeneration can produce paresis phenotypes.

Abnormality of extrapyramidal motor function Orphanet lists extrapyramidal motor involvement, but cached evidence does not resolve the intermediate mechanism.

Show evidence (1 reference)

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla."

This directly supports white matter and motor tract involvement in APBD.

Proteostasis and cellular stress dysregulation

Human APBD lymphoblast proteomics implicates secondary dysregulation of protein ubiquitination, unfolded protein and endoplasmic reticulum stress responses, TOR signaling, glycolysis, and cell death pathways.

protein ubiquitination link ⚠ ABNORMAL response to endoplasmic reticulum stress link ⚠ ABNORMAL TOR signaling link ⚠ ABNORMAL

Show evidence (1 reference)

DOI:10.3389/fneur.2023.1261125 SUPPORT In Vitro

"Bioinformatic analyses indicated multiple canonical pathways and protein–protein interaction networks to be statistically markedly enriched in APBD subjects, including: RNA processing/transport/translation, cell cycle control/replication, mTOR signaling, protein ubiquitination, unfolded protein..."

This lymphoblast proteomics study supports secondary cellular stress and proteostasis pathway dysregulation.

✶

Histopathology

1

Polyglucosan bodies in nervous system and skeletal muscle

APBD is histologically characterized by structurally abnormal glycogen deposits, or polyglucosan bodies, in multiple nervous system and neuromuscular cell types.

Show evidence (1 reference)

PMID:33141444 SUPPORT Human Clinical

"deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies, involving the skeletal muscle, diaphragm, peripheral nerve (including autonomic fibers), brain white matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser extent heart,..."

This clinical review supports polyglucosan body storage across nervous system and skeletal muscle tissues as the characteristic histopathologic feature.

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Pathograph

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Phenotypes

20

Cardiovascular 1

Orthostatic hypotension Orthostatic hypotension (HP:0001278)

Show evidence (1 reference)

PMID:20301758 SUPPORT Other

"autonomic dysfunction (associated with orthostatic hypotension and constipation)"

GeneReviews lists orthostatic hypotension as part of APBD autonomic dysfunction.

Digestive 1

Constipation Constipation (HP:0002019)

Show evidence (1 reference)

PMID:20301758 SUPPORT Other

"autonomic dysfunction (associated with orthostatic hypotension and constipation)"

GeneReviews lists constipation as part of APBD autonomic dysfunction.

Genitourinary 1

Neurogenic bladder VERY_FREQUENT Neurogenic bladder (HP:0000011)

Show evidence (2 references)

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%)."

This directly supports neurogenic bladder as a very frequent APBD phenotype.

ORPHA:206583 SUPPORT Other

"| HP:0000011 | Neurogenic bladder | Very frequent (99-80%) |"

Orphanet lists neurogenic bladder as very frequent.

Integument 1

Skin ulcer FREQUENT Skin ulcer (HP:0200042)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0200042 | Skin ulcer | Frequent (79-30%) |"

Orphanet lists skin ulcer as frequent.

Musculoskeletal 3

Spasticity VERY_FREQUENT Spasticity (HP:0001257)

Show evidence (2 references)

ORPHA:206583 SUPPORT Other

"| HP:0001257 | Spasticity | Very frequent (99-80%) |"

Orphanet lists spasticity as very frequent.

PMID:36796138 SUPPORT Human Clinical

"The adult-onset form of GSD IV, referred to as adult polyglucosan body disease (APBD), is a neurodegenerative disease characterized by neurogenic bladder, spastic paraparesis, and peripheral neuropathy."

This directly supports spastic paraparesis as a characteristic feature.

Muscle weakness VERY_FREQUENT Muscle weakness (HP:0001324)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0001324 | Muscle weakness | Very frequent (99-80%) |"

Orphanet lists muscle weakness as very frequent.

Limitation of joint mobility OCCASIONAL Limitation of joint mobility (HP:0001376)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0001376 | Limitation of joint mobility | Occasional (29-5%) |"

Orphanet lists limitation of joint mobility as occasional.

Nervous System 7

Gait disturbance VERY_FREQUENT Gait disturbance (HP:0001288)

Show evidence (2 references)

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"The median age was 51 years for the onset of neurogenic bladder symptoms, 63 years for wheelchair dependence, and 70 years for death."

Wheelchair dependence supports progressive gait disability in APBD.

ORPHA:206583 SUPPORT Other

"| HP:0001288 | Gait disturbance | Very frequent (99-80%) |"

Orphanet lists gait disturbance as very frequent.

Peripheral neuropathy VERY_FREQUENT Peripheral neuropathy (HP:0009830)

Show evidence (2 references)

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%)."

This directly supports axonal neuropathy as very frequent.

ORPHA:206583 SUPPORT Other

"| HP:0009830 | Peripheral neuropathy | Very frequent (99-80%) |"

Orphanet lists peripheral neuropathy as very frequent.

Dementia OCCASIONAL Dementia (HP:0000726)

Show evidence (2 references)

DOI:10.1002/ana.23598 PARTIAL Human Clinical

"As the disease progressed, mild cognitive decline may have affected up to half of the patients."

This supports acquired cognitive involvement in APBD but does not by itself establish dementia; the dementia frequency is supported by Orphanet.

ORPHA:206583 SUPPORT Other

"| HP:0000726 | Dementia | Occasional (29-5%) |"

Orphanet lists dementia as occasional.

Ataxia OCCASIONAL Ataxia (HP:0001251)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0001251 | Ataxia | Occasional (29-5%) |"

Orphanet lists ataxia as occasional.

Atypical behavior FREQUENT Atypical behavior (HP:0000708)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0000708 | Atypical behavior | Frequent (79-30%) |"

Orphanet lists atypical behavior as frequent.

Intellectual disability VERY_FREQUENT Intellectual disability (HP:0001249)

Show evidence (2 references)

ORPHA:206583 SUPPORT Other

"| HP:0001249 | Intellectual disability | Very frequent (99-80%) |"

Orphanet lists intellectual disability as very frequent.

DOI:10.1002/ana.23598 PARTIAL Human Clinical

"As the disease progressed, mild cognitive decline may have affected up to half of the patients."

The human cohort supports cognitive involvement but describes acquired cognitive decline rather than developmental intellectual disability.

Hemiparesis VERY_FREQUENT Hemiparesis (HP:0001269)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0001269 | Hemiparesis | Very frequent (99-80%) |"

Orphanet lists hemiparesis as very frequent.

Constitutional 1

Urinary incontinence VERY_FREQUENT Urinary incontinence (HP:0000020)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0000020 | Urinary incontinence | Very frequent (99-80%) |"

Orphanet lists urinary incontinence as very frequent.

Other 5

Distal sensory impairment FREQUENT Distal sensory impairment (HP:0002936)

Show evidence (2 references)

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%)."

Vibration loss supports distal sensory impairment in APBD.

ORPHA:206583 SUPPORT Other

"| HP:0002936 | Distal sensory impairment | Frequent (79-30%) |"

Orphanet lists distal sensory impairment as frequent.

Abnormal pyramidal sign VERY_FREQUENT Abnormal pyramidal sign (HP:0007256)

Show evidence (2 references)

DOI:10.1002/ana.23598 SUPPORT Human Clinical

"Neuroimaging showed hyperintense white matter abnormalities on T2 and fluid attenuated inversion recovery sequences predominantly in the periventricular regions, the posterior limb of the internal capsule, the external capsule, and the pyramidal tracts and medial lemniscus of the pons and medulla."

Pyramidal tract imaging abnormalities support pyramidal signs in APBD.

ORPHA:206583 SUPPORT Other

"| HP:0007256 | Abnormal pyramidal sign | Very frequent (99-80%) |"

Orphanet lists abnormal pyramidal signs as very frequent.

Abnormality of extrapyramidal motor function OCCASIONAL Abnormality of extrapyramidal motor function (HP:0002071)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0002071 | Abnormality of extrapyramidal motor function | Occasional (29-5%) |"

Orphanet lists extrapyramidal motor abnormality as occasional.

Urinary bladder sphincter dysfunction VERY_FREQUENT Urinary bladder sphincter dysfunction (HP:0002839)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0002839 | Urinary bladder sphincter dysfunction | Very frequent (99-80%) |"

Orphanet lists urinary bladder sphincter dysfunction as very frequent.

EMG abnormality OCCASIONAL EMG abnormality (HP:0003457)

Show evidence (1 reference)

ORPHA:206583 SUPPORT Other

"| HP:0003457 | EMG abnormality | Occasional (29-5%) |"

Orphanet lists EMG abnormality as occasional.

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Genetic Associations

1

GBE1 (Causative)

Autosomal recessive inheritance

Show evidence (2 references)

ORPHA:206583 SUPPORT Other

"| GBE1 | 1,4-alpha-glucan branching enzyme 1 | hgnc:4180 | Disease-causing germline mutation(s) in |"

Orphanet lists GBE1 as a disease-causing gene for APBD.

PMID:33141444 SUPPORT Human Clinical

"pathogenic variants in GBE1 gene, resulting in deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of polyglucosan bodies"

This directly supports GBE1 as the causal APBD gene.

💊

Treatments

6

Supportive multidisciplinary care

Action: supportive care MAXO:0000950

Supportive management is symptom-directed and includes longitudinal monitoring, functional and neuromusculoskeletal assessment, and care for neurologic, bladder, cardiac, skeletal muscle, liver, and other GSD IV manifestations.

Target Phenotypes: Neurogenic bladder ↗ Gait disturbance ↗

Show evidence (1 reference)

PMID:36796138 SUPPORT Human Clinical

"The educational resource includes practical steps to confirm a GSD IV diagnosis and best practices for medical management, including (a) imaging of the liver, heart, skeletal muscle, brain, and spine, (b) functional and neuromusculoskeletal assessments, (c) laboratory investigations, (d) liver..."

This supports multidisciplinary supportive management and follow-up for GSD IV/APBD.

Physical therapy

Action: physical therapy MAXO:0000011

Individualized physical therapy is recommended to improve flexibility, reduce spasticity, maintain or improve joint mobility, and support activities of daily living.

Target Phenotypes: Spasticity ↗ Limitation of joint mobility ↗ Gait disturbance ↗

Show evidence (1 reference)

PMID:20301758 SUPPORT Other

"An individualized physical therapy program can improve flexibility, reduce spasticity, maintain or improve joint mobility"

GeneReviews recommends individualized physical therapy for flexibility, spasticity, and joint mobility.

Anticholinergic bladder pharmacotherapy

Action: Pharmacotherapy NCIT:C15986

Agent: anticholinergic agent ↗

Anticholinergic drugs may be used as symptom-directed management for spastic bladder in GBE1-APBD.

Target Phenotypes: Neurogenic bladder ↗ Urinary bladder sphincter dysfunction ↗ Urinary incontinence ↗

Show evidence (1 reference)

PMID:20301758 SUPPORT Other

"Spastic bladder may be managed with anticholinergic drugs"

GeneReviews supports anticholinergic drugs for spastic bladder management.

Bladder catheterization

Action: catheterization MAXO:0001389

Clean intermittent catheterization or an indwelling bladder catheter may be used to prevent urosepsis in spastic bladder.

Target Phenotypes: Neurogenic bladder ↗ Urinary bladder sphincter dysfunction ↗ Urinary incontinence ↗

Show evidence (1 reference)

PMID:20301758 SUPPORT Other

"clean intermittent catheterization or an indwelling bladder catheter to prevent urosepsis"

GeneReviews supports catheterization approaches for spastic bladder management.

Genetic counseling

Action: genetic counseling MAXO:0000079

Genetic counseling informs autosomal recessive recurrence risk and options for carrier, prenatal, and preimplantation genetic testing once familial GBE1 variants are known.

Show evidence (1 reference)

PMID:20301758 SUPPORT Other

"GBE1-APBD is inherited in an autosomal recessive manner."

GeneReviews supports genetic counseling for autosomal recessive GBE1-APBD.

Triheptanoin pharmacotherapy trial

Action: Pharmacotherapy NCIT:C15986

Triheptanoin was tested as an anaplerotic therapy for APBD, but the randomized crossover trial did not establish efficacy over six months despite acceptable safety.

Target Phenotypes: Gait disturbance ↗

Show evidence (1 reference)

PMID:29110179 REFUTE Human Clinical

"We cannot conclude that triheptanoin was effective in the treatment of APBD over a 6-month period, but we found it had a good safety profile."

This refutes proven efficacy while documenting the completed treatment trial and safety signal.

🔬

Biochemical Markers

1

Reduced glycogen branching enzyme activity (DECREASED)

Context: Reduced or deficient GBE1 glycogen branching enzyme activity is the proximal biochemical abnormality that drives poorly branched glycogen storage.

Show evidence (1 reference)

PMID:36796138 SUPPORT Human Clinical

"reduced or deficient glycogen branching enzyme activity."

Clinical practice resource identifies deficient glycogen branching enzyme activity in GSD IV/APBD.

🔬

Clinical Trials

1

NCT00947960 PHASE_II COMPLETED

Randomized controlled phase 2 study testing triheptanoin for APBD symptoms.

Target Phenotypes: Gait disturbance ↗

Show evidence (1 reference)

clinicaltrials:NCT00947960 SUPPORT Human Clinical

"The purpose of the study is to determine if triheptanoin is an effective treatment for the symptoms of Adult Polyglucosan Body Disease."

This identifies the APBD triheptanoin interventional trial.

{ }

Source YAML

click to show

name: Adult Polyglucosan Body Disease
creation_date: "2026-05-07T18:30:00Z"
updated_date: "2026-05-19T11:09:57Z"
category: Mendelian
description: >-
  Adult polyglucosan body disease is an autosomal recessive, adult-onset
  GBE1-related glycogen storage disease in which deficient glycogen branching
  enzyme activity causes poorly branched glycogen, polyglucosan body
  accumulation, progressive neurogenic bladder, spastic gait, peripheral
  neuropathy, and variable cognitive decline.
synonyms:
- APBD
- polyglucosan body disease, adult
- polyglucosan body neuropathy, adult form
disease_term:
  preferred_term: adult polyglucosan body disease
  term:
    id: MONDO:0009897
    label: adult polyglucosan body disease
parents:
- glycogen storage disease due to glycogen branching enzyme deficiency
- hereditary peripheral neuropathy
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: >-
    Adult polyglucosan body disease is inherited in an autosomal recessive
    manner due to biallelic pathogenic variants in GBE1.
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "- Autosomal recessive"
    explanation: Orphanet lists autosomal recessive inheritance for APBD.
  - reference: PMID:33141444
    reference_title: "GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Adult polyglucosan body disease (APBD) represents a complex autosomal
      recessive inherited neurometabolic disorder due to homozygous or compound
      heterozygous pathogenic variants in GBE1 gene
    explanation: This review directly states autosomal recessive inheritance and biallelic GBE1 variants.
pathophysiology:
- name: GBE1 deficiency and impaired glycogen branching
  description: >-
    Pathogenic GBE1 variants reduce glycogen branching enzyme activity,
    impairing glycogen synthesis and producing poorly branched glycogen.
  genes:
  - preferred_term: GBE1
    term:
      id: hgnc:4180
      label: GBE1
  biological_processes:
  - preferred_term: glycogen biosynthetic process
    term:
      id: GO:0005978
      label: glycogen biosynthetic process
    modifier: DECREASED
  - preferred_term: glycogen metabolic process
    term:
      id: GO:0005977
      label: glycogen metabolic process
    modifier: ABNORMAL
  molecular_functions:
  - preferred_term: 1,4-alpha-glucan branching enzyme activity
    term:
      id: GO:0003844
      label: 1,4-alpha-glucan branching enzyme activity
    modifier: DECREASED
  chemical_entities:
  - preferred_term: glycogen
    term:
      id: CHEBI:28087
      label: glycogen
    modifier: ABNORMAL
  downstream:
  - target: Polyglucosan body accumulation
    causal_link_type: DIRECT
    description: >-
      Impaired glycogen branching leads to accumulation of poorly branched
      glycogen known as polyglucosan.
  - target: Reduced glycogen branching enzyme activity
    causal_link_type: DIRECT
    description: >-
      Pathogenic GBE1 variants reduce or abolish glycogen branching enzyme
      activity.
    evidence:
    - reference: PMID:36796138
      reference_title: "Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        reduced or deficient glycogen branching enzyme activity.
      explanation: Clinical practice resource identifies reduced or deficient glycogen branching enzyme activity in GSD IV/APBD.
  evidence:
  - reference: PMID:36796138
    reference_title: "Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal
      recessive disorder caused by pathogenic variants in GBE1 which results in
      reduced or deficient glycogen branching enzyme activity.
    explanation: This directly supports GBE1 variants causing reduced glycogen branching enzyme activity.
  - reference: PMID:25665141
    reference_title: Deep intronic GBE1 mutation in manifesting heterozygous patients with adult polyglucosan body disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We identified a deep intronic mutation in this allele,
      GBE1-IVS15+5289_5297delGTGTGGTGGinsTGTTTTTTACATGACAGGT, which acts as a
      gene trap, creating an ectopic last exon.
    explanation: This supports pathogenic GBE1 variants as molecular causes of APBD.
- name: Polyglucosan body accumulation
  description: >-
    Deficient glycogen branching enzyme activity causes storage of abnormal
    glycogen as polyglucosan bodies in central nervous system, peripheral nerve,
    autonomic fibers, and skeletal muscle tissues.
  biological_processes:
  - preferred_term: glycogen metabolic process
    term:
      id: GO:0005977
      label: glycogen metabolic process
    modifier: ABNORMAL
  chemical_entities:
  - preferred_term: poorly branched glycogen
    term:
      id: CHEBI:28087
      label: glycogen
    modifier: INCREASED
  downstream:
  - target: Neurogenic bladder
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Autonomic fiber and nervous system involvement contributes to bladder
      dysfunction.
  - target: Peripheral neuropathy
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Peripheral nerve involvement produces axonal neuropathy and distal sensory
      impairment.
  - target: Peripheral nerve, autonomic, and neuromuscular involvement
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Polyglucosan storage involves peripheral nerve, autonomic fibers, and
      skeletal muscle, providing a shared branch for bladder, neuropathic,
      sensory, EMG, weakness, and mobility-complication phenotypes.
    evidence:
    - reference: PMID:33141444
      reference_title: "GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        deficiency of glycogen-branching enzyme and secondary storage of glycogen
        in the form of polyglucosan bodies, involving the skeletal muscle,
        diaphragm, peripheral nerve (including autonomic fibers), brain white
        matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser
        extent heart, lung, kidney, and liver cells.
      explanation: Clinical review supports peripheral nerve, autonomic, and skeletal muscle involvement downstream of polyglucosan storage.
  - target: Spasticity
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Central motor tract involvement contributes to spastic gait and pyramidal
      signs.
  - target: White matter and motor tract degeneration
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: >-
      Polyglucosan storage involves brain white matter, spinal cord, and
      brainstem motor pathways, connecting storage pathology to white matter and
      motor tract degeneration.
  - target: Proteostasis and cellular stress dysregulation
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: >-
      APBD polyglucosan storage and GBE1 deficiency are associated with secondary
      cellular stress and proteostasis pathway dysregulation in patient-derived
      lymphoblasts.
  evidence:
  - reference: PMID:33141444
    reference_title: "GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      deficiency of glycogen-branching enzyme and secondary storage of glycogen
      in the form of polyglucosan bodies, involving the skeletal muscle,
      diaphragm, peripheral nerve (including autonomic fibers), brain white
      matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser
      extent heart, lung, kidney, and liver cells.
    explanation: This directly supports the affected tissues and polyglucosan storage mechanism.
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Polyglucosan bodies accumulate in the central and peripheral nervous
      systems and are often associated with glycogen branching enzyme (GBE)
      deficiency.
    explanation: This links GBE deficiency to polyglucosan body accumulation in central and peripheral nervous systems.
- name: Peripheral nerve, autonomic, and neuromuscular involvement
  description: >-
    APBD storage pathology affects peripheral nerves, autonomic fibers, nerve
    roots, and skeletal muscle, producing bladder sphincter dysfunction,
    neuropathy with distal sensory impairment, weakness, EMG abnormalities, and
    secondary mobility or skin complications.
  biological_processes:
  - preferred_term: transmission of nerve impulse
    term:
      id: GO:0019226
      label: transmission of nerve impulse
    modifier: ABNORMAL
  evidence:
  - reference: PMID:33141444
    reference_title: "GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      deficiency of glycogen-branching enzyme and secondary storage of glycogen
      in the form of polyglucosan bodies, involving the skeletal muscle,
      diaphragm, peripheral nerve (including autonomic fibers), brain white
      matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser
      extent heart, lung, kidney, and liver cells.
    explanation: Clinical review supports the affected peripheral, autonomic, and neuromuscular tissues.
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common clinical findings were neurogenic bladder (100%), spastic
      paraplegia with vibration loss (90%), and axonal neuropathy (90%).
    explanation: Natural history cohort supports autonomic bladder involvement, vibration loss, and axonal neuropathy.
  - reference: PMID:20301758
    reference_title: "GBE1 Adult Polyglucosan Body Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from
      mixed upper and lower motor neuron involvement, sensory loss predominantly
      in the distal lower extremities, autonomic dysfunction
    explanation: GeneReviews summarizes the same bladder, motor, sensory, and autonomic involvement in classic GBE1-APBD.
  downstream:
  - target: Neurogenic bladder
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Autonomic involvement produces neurogenic bladder.
  - target: Urinary incontinence
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Neurogenic bladder and autonomic dysfunction lead to urinary incontinence.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0000020 | Urinary incontinence | Very frequent (99-80%) |"
      explanation: Orphanet lists urinary incontinence as very frequent in APBD.
  - target: Urinary bladder sphincter dysfunction
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Autonomic and bladder pathway involvement produces bladder sphincter dysfunction.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0002839 | Urinary bladder sphincter dysfunction | Very frequent (99-80%) |"
      explanation: Orphanet lists urinary bladder sphincter dysfunction as very frequent.
  - target: Orthostatic hypotension
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Autonomic dysfunction in classic GBE1-APBD can include orthostatic hypotension.
    evidence:
    - reference: PMID:20301758
      reference_title: "GBE1 Adult Polyglucosan Body Disease."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "autonomic dysfunction (associated with orthostatic hypotension and constipation)"
      explanation: GeneReviews links APBD autonomic dysfunction to orthostatic hypotension.
  - target: Constipation
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Autonomic dysfunction in classic GBE1-APBD can include constipation.
    evidence:
    - reference: PMID:20301758
      reference_title: "GBE1 Adult Polyglucosan Body Disease."
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "autonomic dysfunction (associated with orthostatic hypotension and constipation)"
      explanation: GeneReviews links APBD autonomic dysfunction to constipation.
  - target: Peripheral neuropathy
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Peripheral nerve storage pathology produces axonal neuropathy.
  - target: Distal sensory impairment
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Axonal neuropathy with vibration loss produces distal sensory impairment.
    evidence:
    - reference: DOI:10.1002/ana.23598
      reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        The most common clinical findings were neurogenic bladder (100%),
        spastic paraplegia with vibration loss (90%), and axonal neuropathy
        (90%).
      explanation: Vibration loss in the APBD cohort supports distal sensory impairment.
  - target: Muscle weakness
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Skeletal muscle and neuromuscular involvement can manifest as weakness.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0001324 | Muscle weakness | Very frequent (99-80%) |"
      explanation: Orphanet lists muscle weakness as very frequent.
  - target: EMG abnormality
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Neuromuscular involvement can produce abnormal electromyography.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0003457 | EMG abnormality | Occasional (29-5%) |"
      explanation: Orphanet lists EMG abnormality as occasional.
  - target: Limitation of joint mobility
    causal_link_type: UNKNOWN
    description: Reduced mobility and neuromuscular disease may contribute to joint mobility limitation.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0001376 | Limitation of joint mobility | Occasional (29-5%) |"
      explanation: Orphanet lists limitation of joint mobility as occasional.
  - target: Skin ulcer
    causal_link_type: UNKNOWN
    description: Skin ulcers are modeled as a secondary complication of neuropathy or reduced mobility.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0200042 | Skin ulcer | Frequent (79-30%) |"
      explanation: Orphanet lists skin ulcer as frequent.
- name: White matter and motor tract degeneration
  description: >-
    APBD neuroimaging shows white matter abnormalities and medulla/spinal
    atrophy involving motor tracts, consistent with progressive spastic gait and
    pyramidal signs.
  downstream:
  - target: Gait disturbance
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Abnormal pyramidal sign
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Dementia
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
  - target: Ataxia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Cerebellar and brainstem involvement can produce ataxia.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0001251 | Ataxia | Occasional (29-5%) |"
      explanation: Orphanet lists ataxia as occasional.
  - target: Atypical behavior
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: White matter and cognitive involvement can be accompanied by behavioral changes.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0000708 | Atypical behavior | Frequent (79-30%) |"
      explanation: Orphanet lists atypical behavior as frequent.
  - target: Intellectual disability
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: APBD cognitive involvement is linked conservatively to the Orphanet intellectual disability phenotype.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0001249 | Intellectual disability | Very frequent (99-80%) |"
      explanation: Orphanet lists intellectual disability as very frequent.
  - target: Hemiparesis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Motor tract degeneration can produce paresis phenotypes.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0001269 | Hemiparesis | Very frequent (99-80%) |"
      explanation: Orphanet lists hemiparesis as very frequent.
  - target: Abnormality of extrapyramidal motor function
    causal_link_type: UNKNOWN
    description: Orphanet lists extrapyramidal motor involvement, but cached evidence does not resolve the intermediate mechanism.
    evidence:
    - reference: ORPHA:206583
      reference_title: Adult polyglucosan body disease
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "| HP:0002071 | Abnormality of extrapyramidal motor function | Occasional (29-5%) |"
      explanation: Orphanet lists extrapyramidal motor abnormality as occasional.
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Neuroimaging showed hyperintense white matter abnormalities on T2 and
      fluid attenuated inversion recovery sequences predominantly in the
      periventricular regions, the posterior limb of the internal capsule, the
      external capsule, and the pyramidal tracts and medial lemniscus of the
      pons and medulla.
    explanation: This directly supports white matter and motor tract involvement in APBD.
- name: Proteostasis and cellular stress dysregulation
  description: >-
    Human APBD lymphoblast proteomics implicates secondary dysregulation of
    protein ubiquitination, unfolded protein and endoplasmic reticulum stress
    responses, TOR signaling, glycolysis, and cell death pathways.
  biological_processes:
  - preferred_term: protein ubiquitination
    term:
      id: GO:0016567
      label: protein ubiquitination
    modifier: ABNORMAL
  - preferred_term: response to endoplasmic reticulum stress
    term:
      id: GO:0034976
      label: response to endoplasmic reticulum stress
    modifier: ABNORMAL
  - preferred_term: TOR signaling
    term:
      id: GO:0031929
      label: TOR signaling
    modifier: ABNORMAL
  evidence:
  - reference: DOI:10.3389/fneur.2023.1261125
    reference_title: "Proteomic investigations of adult polyglucosan body disease: insights into the pathobiology of a neurodegenerative disorder"
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Bioinformatic analyses indicated multiple canonical pathways and
      protein–protein interaction networks to be statistically markedly
      enriched in APBD subjects, including: RNA processing/transport/translation,
      cell cycle control/replication, mTOR signaling, protein ubiquitination,
      unfolded protein and endoplasmic reticulum stress responses, glycolysis
      and cell death/apoptosis.
    explanation: This lymphoblast proteomics study supports secondary cellular stress and proteostasis pathway dysregulation.
histopathology:
- name: Polyglucosan bodies in nervous system and skeletal muscle
  finding_term:
    preferred_term: Morphologic Finding
    term:
      id: NCIT:C35867
      label: Morphologic Finding
  description: >-
    APBD is histologically characterized by structurally abnormal glycogen
    deposits, or polyglucosan bodies, in multiple nervous system and
    neuromuscular cell types.
  evidence:
  - reference: PMID:33141444
    reference_title: "GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      deficiency of glycogen-branching enzyme and secondary storage of glycogen
      in the form of polyglucosan bodies, involving the skeletal muscle,
      diaphragm, peripheral nerve (including autonomic fibers), brain white
      matter, spinal cord, nerve roots, cerebellum, brainstem and to a lesser
      extent heart, lung, kidney, and liver cells.
    explanation: >-
      This clinical review supports polyglucosan body storage across nervous
      system and skeletal muscle tissues as the characteristic histopathologic
      feature.
phenotypes:
- category: Genitourinary
  name: Neurogenic bladder
  frequency: VERY_FREQUENT
  description: >-
    Neurogenic bladder is usually the earliest and most penetrant APBD clinical
    manifestation.
  phenotype_term:
    preferred_term: Neurogenic bladder
    term:
      id: HP:0000011
      label: Neurogenic bladder
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common clinical findings were neurogenic bladder (100%), spastic
      paraplegia with vibration loss (90%), and axonal neuropathy (90%).
    explanation: This directly supports neurogenic bladder as a very frequent APBD phenotype.
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0000011 | Neurogenic bladder | Very frequent (99-80%) |"
    explanation: Orphanet lists neurogenic bladder as very frequent.
- category: Genitourinary
  name: Urinary incontinence
  frequency: VERY_FREQUENT
  description: >-
    Urinary incontinence and other bladder sphincter symptoms occur downstream
    of APBD autonomic and central nervous system involvement.
  phenotype_term:
    preferred_term: Urinary incontinence
    term:
      id: HP:0000020
      label: Urinary incontinence
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0000020 | Urinary incontinence | Very frequent (99-80%) |"
    explanation: Orphanet lists urinary incontinence as very frequent.
- category: Neurologic
  name: Spasticity
  frequency: VERY_FREQUENT
  description: >-
    Progressive spasticity and spastic paraparesis are core motor features of
    APBD.
  phenotype_term:
    preferred_term: Spasticity
    term:
      id: HP:0001257
      label: Spasticity
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0001257 | Spasticity | Very frequent (99-80%) |"
    explanation: Orphanet lists spasticity as very frequent.
  - reference: PMID:36796138
    reference_title: "Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The adult-onset form of GSD IV, referred to as adult polyglucosan body
      disease (APBD), is a neurodegenerative disease characterized by neurogenic
      bladder, spastic paraparesis, and peripheral neuropathy.
    explanation: This directly supports spastic paraparesis as a characteristic feature.
- category: Neurologic
  name: Gait disturbance
  frequency: VERY_FREQUENT
  description: >-
    Progressive spastic gait leads to loss of ambulation and wheelchair
    dependence in many patients.
  phenotype_term:
    preferred_term: Gait disturbance
    term:
      id: HP:0001288
      label: Gait disturbance
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The median age was 51 years for the onset of neurogenic bladder symptoms,
      63 years for wheelchair dependence, and 70 years for death.
    explanation: Wheelchair dependence supports progressive gait disability in APBD.
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0001288 | Gait disturbance | Very frequent (99-80%) |"
    explanation: Orphanet lists gait disturbance as very frequent.
- category: Neurologic
  name: Peripheral neuropathy
  frequency: VERY_FREQUENT
  description: >-
    APBD commonly causes axonal peripheral neuropathy with distal sensory loss.
  phenotype_term:
    preferred_term: Peripheral neuropathy
    term:
      id: HP:0009830
      label: Peripheral neuropathy
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common clinical findings were neurogenic bladder (100%), spastic
      paraplegia with vibration loss (90%), and axonal neuropathy (90%).
    explanation: This directly supports axonal neuropathy as very frequent.
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0009830 | Peripheral neuropathy | Very frequent (99-80%) |"
    explanation: Orphanet lists peripheral neuropathy as very frequent.
- category: Neurologic
  name: Distal sensory impairment
  frequency: FREQUENT
  description: >-
    Distal vibration and sensory loss accompanies APBD neuropathy.
  phenotype_term:
    preferred_term: Distal sensory impairment
    term:
      id: HP:0002936
      label: Distal sensory impairment
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The most common clinical findings were neurogenic bladder (100%), spastic
      paraplegia with vibration loss (90%), and axonal neuropathy (90%).
    explanation: Vibration loss supports distal sensory impairment in APBD.
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0002936 | Distal sensory impairment | Frequent (79-30%) |"
    explanation: Orphanet lists distal sensory impairment as frequent.
- category: Neurologic
  name: Abnormal pyramidal sign
  frequency: VERY_FREQUENT
  description: >-
    Pyramidal tract involvement produces upper motor neuron signs and spastic
    paraparesis.
  phenotype_term:
    preferred_term: Abnormal pyramidal sign
    term:
      id: HP:0007256
      label: Abnormal pyramidal sign
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Neuroimaging showed hyperintense white matter abnormalities on T2 and
      fluid attenuated inversion recovery sequences predominantly in the
      periventricular regions, the posterior limb of the internal capsule, the
      external capsule, and the pyramidal tracts and medial lemniscus of the
      pons and medulla.
    explanation: Pyramidal tract imaging abnormalities support pyramidal signs in APBD.
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0007256 | Abnormal pyramidal sign | Very frequent (99-80%) |"
    explanation: Orphanet lists abnormal pyramidal signs as very frequent.
- category: Neurologic
  name: Muscle weakness
  frequency: VERY_FREQUENT
  description: >-
    Weakness may reflect neuromuscular involvement and contributes to mobility
    limitation in APBD.
  phenotype_term:
    preferred_term: Muscle weakness
    term:
      id: HP:0001324
      label: Muscle weakness
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0001324 | Muscle weakness | Very frequent (99-80%) |"
    explanation: Orphanet lists muscle weakness as very frequent.
- category: Neurologic
  name: Dementia
  frequency: OCCASIONAL
  description: >-
    Cognitive decline can progress to dementia in a subset of adults with APBD.
  phenotype_term:
    preferred_term: Dementia
    term:
      id: HP:0000726
      label: Dementia
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      As the disease progressed, mild cognitive decline may have affected up to
      half of the patients.
    explanation: >-
      This supports acquired cognitive involvement in APBD but does not by itself
      establish dementia; the dementia frequency is supported by Orphanet.
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0000726 | Dementia | Occasional (29-5%) |"
    explanation: Orphanet lists dementia as occasional.
- category: Neurologic
  name: Ataxia
  frequency: OCCASIONAL
  description: >-
    Ataxia is reported less often than spastic gait, bladder dysfunction, and
    neuropathy.
  phenotype_term:
    preferred_term: Ataxia
    term:
      id: HP:0001251
      label: Ataxia
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0001251 | Ataxia | Occasional (29-5%) |"
    explanation: Orphanet lists ataxia as occasional.
- category: Neurobehavioral
  name: Atypical behavior
  frequency: FREQUENT
  description: >-
    Behavioral or psychiatric changes may accompany APBD cognitive involvement.
  phenotype_term:
    preferred_term: Atypical behavior
    term:
      id: HP:0000708
      label: Atypical behavior
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0000708 | Atypical behavior | Frequent (79-30%) |"
    explanation: Orphanet lists atypical behavior as frequent.
- category: Neurologic
  name: Intellectual disability
  frequency: VERY_FREQUENT
  description: >-
    Orphanet maps APBD cognitive involvement to intellectual disability, while
    the natural history cohort more specifically describes adult cognitive
    decline.
  phenotype_term:
    preferred_term: Intellectual disability
    term:
      id: HP:0001249
      label: Intellectual disability
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0001249 | Intellectual disability | Very frequent (99-80%) |"
    explanation: Orphanet lists intellectual disability as very frequent.
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      As the disease progressed, mild cognitive decline may have affected up to
      half of the patients.
    explanation: >-
      The human cohort supports cognitive involvement but describes acquired
      cognitive decline rather than developmental intellectual disability.
- category: Neurologic
  name: Hemiparesis
  frequency: VERY_FREQUENT
  description: >-
    Orphanet lists hemiparesis among APBD motor phenotypes; clinically, APBD
    more often presents with progressive spastic paraparesis and gait
    impairment.
  phenotype_term:
    preferred_term: Hemiparesis
    term:
      id: HP:0001269
      label: Hemiparesis
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0001269 | Hemiparesis | Very frequent (99-80%) |"
    explanation: Orphanet lists hemiparesis as very frequent.
- category: Musculoskeletal
  name: Limitation of joint mobility
  frequency: OCCASIONAL
  description: >-
    Limitation of joint mobility may occur as a secondary musculoskeletal
    complication in APBD.
  phenotype_term:
    preferred_term: Limitation of joint mobility
    term:
      id: HP:0001376
      label: Limitation of joint mobility
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0001376 | Limitation of joint mobility | Occasional (29-5%) |"
    explanation: Orphanet lists limitation of joint mobility as occasional.
- category: Neurologic
  name: Abnormality of extrapyramidal motor function
  frequency: OCCASIONAL
  description: >-
    Extrapyramidal motor findings are listed less often than pyramidal signs
    and spastic gait.
  phenotype_term:
    preferred_term: Abnormality of extrapyramidal motor function
    term:
      id: HP:0002071
      label: Abnormality of extrapyramidal motor function
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0002071 | Abnormality of extrapyramidal motor function | Occasional (29-5%) |"
    explanation: Orphanet lists extrapyramidal motor abnormality as occasional.
- category: Genitourinary
  name: Urinary bladder sphincter dysfunction
  frequency: VERY_FREQUENT
  description: >-
    Bladder sphincter dysfunction is part of the neurogenic bladder/autonomic
    phenotype in APBD.
  phenotype_term:
    preferred_term: Urinary bladder sphincter dysfunction
    term:
      id: HP:0002839
      label: Urinary bladder sphincter dysfunction
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0002839 | Urinary bladder sphincter dysfunction | Very frequent (99-80%) |"
    explanation: Orphanet lists urinary bladder sphincter dysfunction as very frequent.
- category: Cardiovascular
  name: Orthostatic hypotension
  description: >-
    Orthostatic hypotension can occur as part of APBD autonomic dysfunction.
  phenotype_term:
    preferred_term: Orthostatic hypotension
    term:
      id: HP:0001278
      label: Orthostatic hypotension
  evidence:
  - reference: PMID:20301758
    reference_title: "GBE1 Adult Polyglucosan Body Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "autonomic dysfunction (associated with orthostatic hypotension and constipation)"
    explanation: GeneReviews lists orthostatic hypotension as part of APBD autonomic dysfunction.
- category: Gastrointestinal
  name: Constipation
  description: Constipation can occur as part of APBD autonomic dysfunction.
  phenotype_term:
    preferred_term: Constipation
    term:
      id: HP:0002019
      label: Constipation
  evidence:
  - reference: PMID:20301758
    reference_title: "GBE1 Adult Polyglucosan Body Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "autonomic dysfunction (associated with orthostatic hypotension and constipation)"
    explanation: GeneReviews lists constipation as part of APBD autonomic dysfunction.
- category: Neurologic
  name: EMG abnormality
  frequency: OCCASIONAL
  description: >-
    Electromyography may be abnormal in APBD neuromuscular presentations.
  phenotype_term:
    preferred_term: EMG abnormality
    term:
      id: HP:0003457
      label: EMG abnormality
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0003457 | EMG abnormality | Occasional (29-5%) |"
    explanation: Orphanet lists EMG abnormality as occasional.
- category: Dermatological
  name: Skin ulcer
  frequency: FREQUENT
  description: >-
    Skin ulceration is listed by Orphanet and may reflect complications of
    neuropathy or reduced mobility.
  phenotype_term:
    preferred_term: Skin ulcer
    term:
      id: HP:0200042
      label: Skin ulcer
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| HP:0200042 | Skin ulcer | Frequent (79-30%) |"
    explanation: Orphanet lists skin ulcer as frequent.
biochemical:
- name: Reduced glycogen branching enzyme activity
  presence: DECREASED
  context: >-
    Reduced or deficient GBE1 glycogen branching enzyme activity is the proximal
    biochemical abnormality that drives poorly branched glycogen storage.
  evidence:
  - reference: PMID:36796138
    reference_title: "Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      reduced or deficient glycogen branching enzyme activity.
    explanation: Clinical practice resource identifies deficient glycogen branching enzyme activity in GSD IV/APBD.
genetic:
- name: GBE1
  association: Causative
  gene_term:
    preferred_term: GBE1
    term:
      id: hgnc:4180
      label: GBE1
  inheritance:
  - name: Autosomal recessive inheritance
  evidence:
  - reference: ORPHA:206583
    reference_title: Adult polyglucosan body disease
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "| GBE1 | 1,4-alpha-glucan branching enzyme 1 | hgnc:4180 | Disease-causing germline mutation(s) in |"
    explanation: Orphanet lists GBE1 as a disease-causing gene for APBD.
  - reference: PMID:33141444
    reference_title: "GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      pathogenic variants in GBE1 gene, resulting in deficiency of
      glycogen-branching enzyme and secondary storage of glycogen in the form of
      polyglucosan bodies
    explanation: This directly supports GBE1 as the causal APBD gene.
diagnosis:
- name: GBE1 molecular genetic testing
  description: >-
    Molecular testing for biallelic GBE1 pathogenic variants confirms the
    diagnosis and can identify deep intronic founder alleles missed by exon-only
    testing.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
    qualifiers:
    - predicate:
        preferred_term: has participant
        term:
          id: RO:0000057
          label: has participant
      value:
        preferred_term: GBE1
        term:
          id: hgnc:4180
          label: GBE1
  results: Biallelic pathogenic GBE1 variants.
  evidence:
  - reference: PMID:25665141
    reference_title: Deep intronic GBE1 mutation in manifesting heterozygous patients with adult polyglucosan body disease.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      When we reverse transcribed and sequenced the mRNA of GBE1, we found that
      all manifesting heterozygous patients had the c.986A>C mutant mRNA and
      complete lack of mRNA encoded by the second allele.
    explanation: This supports GBE1 molecular testing, including RNA-level analysis for deep intronic variants.
- name: Brain and spine magnetic resonance imaging
  description: >-
    Brain and spine MRI can show characteristic white matter abnormalities,
    pyramidal tract involvement, and universal medulla/spinal atrophy.
  diagnosis_term:
    preferred_term: magnetic resonance imaging procedure
    term:
      id: MAXO:0000424
      label: magnetic resonance imaging procedure
  results: T2/FLAIR white matter abnormalities and medulla/spinal atrophy.
  evidence:
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Brain and spine magnetic resonance images were reviewed in 44 patients.
    explanation: This supports brain and spine MRI as a diagnostic assessment in the natural history cohort.
  - reference: DOI:10.1002/ana.23598
    reference_title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Atrophy of the medulla and spine was universal.
    explanation: This supports medulla and spinal atrophy as a characteristic MRI finding.
treatments:
- name: Supportive multidisciplinary care
  description: >-
    Supportive management is symptom-directed and includes longitudinal
    monitoring, functional and neuromusculoskeletal assessment, and care for
    neurologic, bladder, cardiac, skeletal muscle, liver, and other GSD IV
    manifestations.
  treatment_term:
    preferred_term: supportive care
    term:
      id: MAXO:0000950
      label: supportive care
  target_phenotypes:
  - preferred_term: Neurogenic bladder
    term:
      id: HP:0000011
      label: Neurogenic bladder
  - preferred_term: Gait disturbance
    term:
      id: HP:0001288
      label: Gait disturbance
  evidence:
  - reference: PMID:36796138
    reference_title: "Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The educational resource includes practical steps to confirm a GSD IV
      diagnosis and best practices for medical management, including (a) imaging
      of the liver, heart, skeletal muscle, brain, and spine, (b) functional and
      neuromusculoskeletal assessments, (c) laboratory investigations, (d) liver
      and heart transplantation, and (e) long-term follow-up care.
    explanation: This supports multidisciplinary supportive management and follow-up for GSD IV/APBD.
- name: Physical therapy
  description: >-
    Individualized physical therapy is recommended to improve flexibility,
    reduce spasticity, maintain or improve joint mobility, and support
    activities of daily living.
  treatment_term:
    preferred_term: physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
  target_phenotypes:
  - preferred_term: Spasticity
    term:
      id: HP:0001257
      label: Spasticity
  - preferred_term: Limitation of joint mobility
    term:
      id: HP:0001376
      label: Limitation of joint mobility
  - preferred_term: Gait disturbance
    term:
      id: HP:0001288
      label: Gait disturbance
  evidence:
  - reference: PMID:20301758
    reference_title: "GBE1 Adult Polyglucosan Body Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      An individualized physical therapy program can improve flexibility, reduce
      spasticity, maintain or improve joint mobility
    explanation: GeneReviews recommends individualized physical therapy for flexibility, spasticity, and joint mobility.
- name: Anticholinergic bladder pharmacotherapy
  description: >-
    Anticholinergic drugs may be used as symptom-directed management for spastic
    bladder in GBE1-APBD.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: anticholinergic agent
      term:
        id: NCIT:C66880
        label: Anticholinergic Agent
  target_phenotypes:
  - preferred_term: Neurogenic bladder
    term:
      id: HP:0000011
      label: Neurogenic bladder
  - preferred_term: Urinary bladder sphincter dysfunction
    term:
      id: HP:0002839
      label: Urinary bladder sphincter dysfunction
  - preferred_term: Urinary incontinence
    term:
      id: HP:0000020
      label: Urinary incontinence
  evidence:
  - reference: PMID:20301758
    reference_title: "GBE1 Adult Polyglucosan Body Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Spastic bladder may be managed with anticholinergic drugs"
    explanation: GeneReviews supports anticholinergic drugs for spastic bladder management.
- name: Bladder catheterization
  description: >-
    Clean intermittent catheterization or an indwelling bladder catheter may be
    used to prevent urosepsis in spastic bladder.
  treatment_term:
    preferred_term: catheterization
    term:
      id: MAXO:0001389
      label: catheterization
  target_phenotypes:
  - preferred_term: Neurogenic bladder
    term:
      id: HP:0000011
      label: Neurogenic bladder
  - preferred_term: Urinary bladder sphincter dysfunction
    term:
      id: HP:0002839
      label: Urinary bladder sphincter dysfunction
  - preferred_term: Urinary incontinence
    term:
      id: HP:0000020
      label: Urinary incontinence
  evidence:
  - reference: PMID:20301758
    reference_title: "GBE1 Adult Polyglucosan Body Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "clean intermittent catheterization or an indwelling bladder catheter to prevent urosepsis"
    explanation: GeneReviews supports catheterization approaches for spastic bladder management.
- name: Genetic counseling
  description: >-
    Genetic counseling informs autosomal recessive recurrence risk and options
    for carrier, prenatal, and preimplantation genetic testing once familial
    GBE1 variants are known.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: PMID:20301758
    reference_title: "GBE1 Adult Polyglucosan Body Disease."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "GBE1-APBD is inherited in an autosomal recessive manner."
    explanation: GeneReviews supports genetic counseling for autosomal recessive GBE1-APBD.
- name: Triheptanoin pharmacotherapy trial
  description: >-
    Triheptanoin was tested as an anaplerotic therapy for APBD, but the
    randomized crossover trial did not establish efficacy over six months
    despite acceptable safety.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  target_phenotypes:
  - preferred_term: Gait disturbance
    term:
      id: HP:0001288
      label: Gait disturbance
  evidence:
  - reference: PMID:29110179
    reference_title: A double-blind, placebo-controlled trial of triheptanoin in adult polyglucosan body disease and open-label, long-term outcome.
    supports: REFUTE
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We cannot conclude that triheptanoin was effective in the treatment of
      APBD over a 6-month period, but we found it had a good safety profile.
    explanation: This refutes proven efficacy while documenting the completed treatment trial and safety signal.
clinical_trials:
- name: NCT00947960
  phase: PHASE_II
  status: COMPLETED
  description: >-
    Randomized controlled phase 2 study testing triheptanoin for APBD symptoms.
  target_phenotypes:
  - preferred_term: Gait disturbance
    term:
      id: HP:0001288
      label: Gait disturbance
  evidence:
  - reference: clinicaltrials:NCT00947960
    reference_title: A Treatment Trial of Triheptanoin in Patients With Adult Polyglucosan Body Disease - A Randomized Controlled Study
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The purpose of the study is to determine if triheptanoin is an effective
      treatment for the symptoms of Adult Polyglucosan Body Disease.
    explanation: This identifies the APBD triheptanoin interventional trial.
datasets: []
references:
- reference: ORPHA:206583
  title: Adult polyglucosan body disease
  findings:
  - statement: >-
      Adult polyglucosan body disease is an autosomal recessive GBE1-related
      adult glycogen storage disease with neurogenic bladder, spasticity,
      neuropathy, and cognitive involvement.
    supporting_text: >-
      A glycogen storage disease of adults characterized by progressive upper
      and lower motor neuron dysfunction, progressive neurogenic bladder and
      cognitive difficulties that can lead to dementia.
- reference: PMID:20301758
  title: GBE1 Adult Polyglucosan Body Disease.
  tags:
  - GeneReviews
  findings:
  - statement: >-
      GeneReviews summarizes classic GBE1-APBD as adult-onset neurogenic
      bladder, gait difficulty from spasticity and weakness, distal sensory
      loss, autonomic dysfunction, and mild cognitive difficulty.
    supporting_text: >-
      Most individuals with classic GBE1 adult polyglucosan body disease
      (GBE1-APBD) present after age 40 years with unexplained progressive
      neurogenic bladder, gait difficulties (i.e., spasticity and weakness)
      from mixed upper and lower motor neuron involvement, sensory loss
      predominantly in the distal lower extremities, autonomic dysfunction
      (associated with orthostatic hypotension and constipation), and mild
      cognitive difficulties (often executive dysfunction).
- reference: DOI:10.1002/ana.23598
  title: "Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings"
  findings:
  - statement: >-
      The 50-patient natural history cohort defines neurogenic bladder, spastic
      paraplegia with vibration loss, axonal neuropathy, and characteristic MRI
      findings as core APBD features.
    supporting_text: >-
      The most common clinical findings were neurogenic bladder (100%), spastic
      paraplegia with vibration loss (90%), and axonal neuropathy (90%).
- reference: PMID:33141444
  title: "GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes."
  findings:
  - statement: >-
      APBD is caused by biallelic GBE1 pathogenic variants with deficient
      glycogen branching enzyme activity and polyglucosan storage across
      neuromuscular and nervous system tissues.
    supporting_text: >-
      Adult polyglucosan body disease (APBD) represents a complex autosomal
      recessive inherited neurometabolic disorder due to homozygous or compound
      heterozygous pathogenic variants in GBE1 gene, resulting in deficiency of
      glycogen-branching enzyme and secondary storage of glycogen in the form of
      polyglucosan bodies
- reference: PMID:36796138
  title: "Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource."
  findings:
  - statement: >-
      Expert clinical practice recommendations support diagnosis and
      multidisciplinary management for GSD IV phenotypes including APBD.
    supporting_text: >-
      The educational resource includes practical steps to confirm a GSD IV
      diagnosis and best practices for medical management
- reference: PMID:29110179
  title: A double-blind, placebo-controlled trial of triheptanoin in adult polyglucosan body disease and open-label, long-term outcome.
  findings:
  - statement: >-
      Triheptanoin was safe and tolerated but did not establish efficacy over a
      six-month randomized crossover treatment period.
    supporting_text: >-
      We cannot conclude that triheptanoin was effective in the treatment of
      APBD over a 6-month period, but we found it had a good safety profile.

📚

References & Deep Research

References

6

ORPHA:206583

Adult polyglucosan body disease

1 finding

Adult polyglucosan body disease is an autosomal recessive GBE1-related adult glycogen storage disease with neurogenic bladder, spasticity, neuropathy, and cognitive involvement.

"A glycogen storage disease of adults characterized by progressive upper and lower motor neuron dysfunction, progressive neurogenic bladder and cognitive difficulties that can lead to dementia."

PMID:20301758

GBE1 Adult Polyglucosan Body Disease.

1 finding

GeneReviews summarizes classic GBE1-APBD as adult-onset neurogenic bladder, gait difficulty from spasticity and weakness, distal sensory loss, autonomic dysfunction, and mild cognitive difficulty.

"Most individuals with classic GBE1 adult polyglucosan body disease (GBE1-APBD) present after age 40 years with unexplained progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the..."

DOI:10.1002/ana.23598

Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings

1 finding

The 50-patient natural history cohort defines neurogenic bladder, spastic paraplegia with vibration loss, axonal neuropathy, and characteristic MRI findings as core APBD features.

"The most common clinical findings were neurogenic bladder (100%), spastic paraplegia with vibration loss (90%), and axonal neuropathy (90%)."

PMID:33141444

GBE1-related disorders: Adult polyglucosan body disease and its neuromuscular phenotypes.

1 finding

APBD is caused by biallelic GBE1 pathogenic variants with deficient glycogen branching enzyme activity and polyglucosan storage across neuromuscular and nervous system tissues.

"Adult polyglucosan body disease (APBD) represents a complex autosomal recessive inherited neurometabolic disorder due to homozygous or compound heterozygous pathogenic variants in GBE1 gene, resulting in deficiency of glycogen-branching enzyme and secondary storage of glycogen in the form of..."

PMID:36796138

Diagnosis and management of glycogen storage disease type IV, including adult polyglucosan body disease: A clinical practice resource.

1 finding

Expert clinical practice recommendations support diagnosis and multidisciplinary management for GSD IV phenotypes including APBD.

"The educational resource includes practical steps to confirm a GSD IV diagnosis and best practices for medical management"

PMID:29110179

A double-blind, placebo-controlled trial of triheptanoin in adult polyglucosan body disease and open-label, long-term outcome.

1 finding

Triheptanoin was safe and tolerated but did not establish efficacy over a six-month randomized crossover treatment period.

"We cannot conclude that triheptanoin was effective in the treatment of APBD over a 6-month period, but we found it had a good safety profile."

Deep Research

1

Adult Polyglucosan Body Disease Deep Research Fallback ▸

Adult Polyglucosan Body Disease Deep Research Fallback

Date: 2026-05-07

Provider Attempts

Falcon provider: timeout 120s just research-disorder falcon Adult_Polyglucosan_Body_Disease timed out with no usable artifact.
OpenAI provider: timeout 120s just research-disorder openai Adult_Polyglucosan_Body_Disease timed out with no usable artifact.

Evidence Scope Used For Curation

The YAML curation was completed from regenerated Orphanet cache and cached primary literature:

ORPHA:206583: Orphanet structured record for APBD definition, inheritance, GBE1 gene association, prevalence, and phenotype frequencies.
DOI:10.1002/ana.23598: 50-patient APBD natural history and MRI cohort supporting neurogenic bladder, spastic paraplegia, axonal neuropathy, cognitive decline, GBE1 mutation data, and characteristic brain/spine MRI findings.
PMID:33141444: GBE1-related disorders review supporting APBD inheritance, GBE1 causality, glycogen branching enzyme deficiency, polyglucosan body storage, and neuromuscular phenotypic spectrum.
PMID:36796138: clinical practice resource for diagnosis and management of GSD IV/APBD.
PMID:25665141: deep intronic GBE1 variant evidence supporting molecular genetic testing and GBE1 causality.
DOI:10.3389/fneur.2023.1261125: APBD proteomics study supporting secondary proteostasis and cellular stress pathway dysregulation.
PMID:29110179 and clinicaltrials:NCT00947960: triheptanoin randomized crossover trial and registry evidence, including lack of demonstrated efficacy over six months.

Adult Polyglucosan Body Disease

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References

Deep Research

Adult Polyglucosan Body Disease Deep Research Fallback

Provider Attempts

Evidence Scope Used For Curation