👪

Inheritance

1

Autosomal recessive inheritance HP:0000007

Caused by biallelic loss-of-function variants in GYG1 (glycogenin-1).

Autosomal recessive inheritance

◆

Subtypes

2

Glycogen storage disease XV (cardiac presentation) MONDO:0013291

Presentation dominated by cardiomyopathy and arrhythmia, associated with expression of a nonfunctional glycogenin-1 in the heart and storage of abnormal glycogen; skeletal muscle may show glycogen depletion.

Polyglucosan body myopathy type 2 (skeletal presentation) MONDO:0014526

Adult-onset, slowly progressive limb-girdle skeletal myopathy with accumulation of glycogen and polyglucosan in muscle fibers, typically without cardiomyopathy.

?

Discussions and Knowledge Gaps

2

Does expression of a mutant glycogenin-1 in the heart actually cause the cardiomyopathy, or is it only associated with it?

KNOWLEDGE GAP mutant_glycogenin1_cardiomyopathy_causation

Attached to

pathophysiology#Mutant Glycogenin-1 Cardiotoxicity

The cardiac phenotype tracks with expression of a nonfunctional glycogenin-1 rather than with loss of glycogenin-1 as such: patients who completely lack the protein from biallelic truncating variants do not develop cardiomyopathy. Whether the mutant protein is itself sufficient to cause the cardiomyopathy is not settled.

Show evidence (1 reference)

PMID:31628455 SUPPORT Human Clinical

"An important question is whether expression of mutated glycogenin-1 does in fact cause cardiomyopathy since patients who completely lack glycogenin-1 because of biallelic truncating GYG1 mutations do not develop cardiomyopathy"

The source explicitly leaves cardiomyopathy causation open and distinguishes truncating from missense alleles.

Why does loss of glycogenin-1 lead to accumulation of abnormal, poorly branched polyglucosan rather than simply less glycogen?

KNOWLEDGE GAP why_polyglucosan_forms

Attached to

pathophysiology#Polyglucosan and Glycogen Accumulation in Skeletal Muscle

Glycogen is still synthesized without glycogenin-1, but the product is abnormal. An imbalance between glycogen synthase and branching enzyme activity has been proposed, but the mechanism linking loss of priming to polyglucosan is not established.

Show evidence (1 reference)

PMID:26652229 SUPPORT Human Clinical

"the cause of polyglucosan accumulation remains difficult to understand"

The source states directly that the basis of polyglucosan accumulation is unresolved.

⚙

Pathophysiology

5

GYG1 Loss of Function

Biallelic GYG1 variants either abolish glycogenin-1 (truncating alleles) or yield a nonfunctional protein (missense alleles).

Downstream

Impaired Glycogenin-1 Autoglucosylation Absent or nonfunctional glycogenin-1 cannot prime glycogen synthesis normally.

Show evidence (1 reference)

PMID:31628455 SUPPORT REVIEW SYNTHESIS Human Clinical

"Patients with GYG1 mutations are characterized by either the absence of glycogenin-1 or the expression of nonfunctional glycogenin-1, and there is storage of glycogen and polyglucosan in the affected tissues."

States the two molecular consequences of GYG1 variants.

Impaired Glycogenin-1 Autoglucosylation

Glycogenin-1 normally autoglucosylates to build the short oligosaccharide primer that glycogen synthase and branching enzyme extend into glycogen. Loss of this priming activity disrupts normal glycogen synthesis in muscle.

GYG1 hgnc:4699

glycogenin glucosyltransferase activity GO:0008466 ↓ DECREASED

Downstream

Polyglucosan and Glycogen Accumulation in Skeletal Muscle In skeletal muscle, loss of glycogenin-1 leads to focal storage of glycogen and polyglucosan.

Skeletal Muscle Glycogen Depletion In the founding case, inactivated priming instead depleted glycogen in skeletal muscle.

Mutant Glycogenin-1 Cardiotoxicity A nonfunctional glycogenin-1 expressed in the heart is deleterious and stores abnormal glycogen.

Show evidence (2 references)

PMID:20357282 SUPPORT Human Clinical

"The missense mutation resulted in inactivation of the autoglucosylation of glycogenin-1 that is necessary for the priming of glycogen synthesis in muscle."

Identifies loss of glycogenin-1 autoglucosylation as the molecular lesion.

PMID:31628455 SUPPORT Human Clinical

"Glycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2."

Clarifies that glycogen synthesis is not abolished without glycogenin-1 and is not rescued by glycogenin-2, so the lesion is abnormal rather than absent synthesis.

Polyglucosan and Glycogen Accumulation in Skeletal Muscle

In skeletal muscle, absent glycogenin-1 leads to focal accumulation of glycogen and abnormal, poorly branched polyglucosan in muscle fibers.

skeletal muscle fiber CL:0008002

skeletal muscle tissue UBERON:0001134

Downstream

Skeletal myopathy Polyglucosan and glycogen deposits disrupt muscle fibers, causing progressive weakness.

Limb-girdle muscle weakness The myopathy manifests as progressive limb-girdle weakness.

Exercise intolerance Exercise intolerance is reported in the polyglucosan myopathy.

Show evidence (1 reference)

PMID:31628455 SUPPORT Human Clinical

"Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers."

Supports skeletal-muscle storage of glycogen and polyglucosan as the consequence of glycogenin-1 absence.

Skeletal Muscle Glycogen Depletion

In the cardiac/missense pole (the founding GSD XV case), inactivated glycogenin-1 priming instead depletes glycogen in skeletal muscle, with a shift toward slow-twitch oxidative fibers.

skeletal muscle fiber CL:0008002

skeletal muscle tissue UBERON:0001134

Downstream

Muscle weakness Muscle weakness accompanies the skeletal glycogen depletion in this pole.

Type 1 muscle fiber predominance The depleted muscle shows a shift toward slow-twitch oxidative fibers.

Show evidence (1 reference)

PMID:20357282 SUPPORT Human Clinical

"muscle weakness, associated with the depletion of glycogen in skeletal muscle"

Documents skeletal-muscle glycogen depletion in the founding case, the pole opposite to polyglucosan storage.

Mutant Glycogenin-1 Cardiotoxicity

When a nonfunctional (missense) glycogenin-1 is expressed in the heart it is deleterious, with storage of abnormal glycogen and cardiomyopathy. Whether the mutant protein is itself sufficient to cause the cardiomyopathy is unresolved, since patients who completely lack glycogenin-1 do not develop it (see discussions).

cardiac muscle cell CL:0000746

cardiac muscle tissue UBERON:0001133

Downstream

Cardiomyopathy Storage of abnormal glycogen in cardiomyocytes produces cardiomyopathy.

Arrhythmia Abnormal cardiac storage material is associated with conduction disturbance.

Show evidence (1 reference)

PMID:31628455 SUPPORT Human Clinical

"Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy."

Supports a deleterious mutant glycogenin-1 in the heart as the driver of cardiomyopathy.

✶

Histopathology

1

Polyglucosan bodies in muscle

Subsarcolemmal and intermyofibrillar deposits that are PAS-positive and partially diastase (alpha-amylase) resistant, consistent with polyglucosan.

Show evidence (1 reference)

PMID:26652229 SUPPORT Human Clinical

"PAS-positive deposits consistent with polyglucosan"

Describes the diagnostic polyglucosan deposits on muscle biopsy.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

8

Cardiovascular 3

Cardiomyopathy HP:0001638

Sequelae: Congestive heart failure

Show evidence (1 reference)

PMID:31628455 SUPPORT Human Clinical

"Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy."

Supports cardiomyopathy as a consequence of mutant glycogenin-1 in the heart.

Arrhythmia HP:0011675

Show evidence (1 reference)

PMID:20357282 SUPPORT Human Clinical

"cardiac arrhythmia, associated with the accumulation of abnormal storage material in the heart"

Documents arrhythmia with abnormal cardiac storage in the index patient.

Congestive heart failure HP:0001635

Show evidence (1 reference)

PMID:31628455 SUPPORT Human Clinical

"Cardiac failure with reduced ejection fraction. Cardiac arrhythmias."

Documents cardiac failure with reduced ejection fraction in a GYG1 cardiomyopathy patient.

Limbs 1

Limb-girdle muscle weakness HP:0003325

Show evidence (1 reference)

PMID:26652229 SUPPORT Human Clinical

"Five Sardinian patients presented in their 5th or 6th decade with progressive limb girdle muscle weakness"

Documents late-onset progressive limb-girdle weakness in a GYG1 cohort.

Musculoskeletal 3

Skeletal myopathy HP:0003198

Show evidence (1 reference)

PMID:31628455 SUPPORT REVIEW SYNTHESIS Human Clinical

"Most of these patients had adult-onset, slowly progressive myopathy and muscle weakness without cardiomyopathy"

Supports the dominant adult-onset skeletal myopathy presentation.

Muscle weakness HP:0001324

Show evidence (1 reference)

PMID:20357282 SUPPORT Human Clinical

"muscle weakness, associated with the depletion of glycogen in skeletal muscle"

Documents muscle weakness with skeletal glycogen depletion in the founding case.

Type 1 muscle fiber predominance HP:0003803

Show evidence (1 reference)

PMID:20357282 SUPPORT Human Clinical

"The skeletal muscle showed a marked predominance of slow-twitch, oxidative muscle fibers and mitochondrial proliferation."

Documents the slow-twitch oxidative fiber predominance in the founding case.

Constitutional 1

Exercise intolerance HP:0003546

Show evidence (1 reference)

PMID:26652229 SUPPORT Human Clinical

"Exercise intolerance is a relatively new clinical finding of GYG1-related polyglucosan body myopathy"

Documents exercise intolerance as a feature of the polyglucosan myopathy.

🧬

Genetic Associations

1

GYG1

Gene: GYG1 hgnc:4699 relationship_type: CAUSATIVE

Show evidence (2 references)

PMID:31628455 SUPPORT REVIEW SYNTHESIS Human Clinical

"Glycogen storage disease type XV/polyglucosan body myopathy 2 (OMIM#613507/#616199) is caused by biallelic mutations in the GYG1 gene."

Establishes biallelic GYG1 variants as the cause of both named presentations.

PMID:20357282 SUPPORT Human Clinical

"Sequencing of the glycogenin-1 gene, GYG1, revealed a nonsense mutation in one allele and a missense mutation, Thr83Met, in the other."

Documents biallelic GYG1 variants in the index patient, consistent with recessive inheritance.

💊

Medical Actions

2

Supportive care

Action: Supportive Care NCIT:C15747

Management is symptomatic: surveillance and treatment of cardiomyopathy and arrhythmia, and management of progressive muscle weakness.

Cardiac transplantation

Action: Heart Transplantation NCIT:C15246

Heart transplantation for advanced, decompensated cardiomyopathy.

Mechanism Target:

Congestive heart failure — Transplantation replaces the failing heart in end-stage cardiac disease.

Show evidence (1 reference)

PMID:31628455 SUPPORT Human Clinical

"Cardiac failure. Heart transplantation at age 48"

Documents heart transplantation for cardiac failure in a GYG1 patient.

🔬

Diagnosis

4

Muscle biopsy

Muscle biopsy showing PAS-positive, diastase-resistant polyglucosan deposits (storage pole) or glycogen depletion (depletion pole).

Show evidence (1 reference)

PMID:26652229 SUPPORT Human Clinical

"PAS-positive deposits consistent with polyglucosan"

Muscle-biopsy polyglucosan deposits are the histological basis of diagnosis.

Glycogenin-1 protein testing

Western blot or immunohistochemistry showing absent or unglucosylated glycogenin-1 in muscle and heart.

Show evidence (1 reference)

PMID:20357282 SUPPORT Human Clinical

"Western blotting showed the presence of unglucosylated glycogenin-1 in the muscle and heart."

Protein-level demonstration of unglucosylated glycogenin-1 supports the diagnosis.

GYG1 molecular testing

Sequencing of GYG1 to identify biallelic pathogenic variants confirms the diagnosis.

Show evidence (1 reference)

PMID:20357282 SUPPORT Human Clinical

"Sequencing of the glycogenin-1 gene, GYG1, revealed a nonsense mutation in one allele and a missense mutation, Thr83Met, in the other."

Biallelic GYG1 variants on sequencing establish the molecular diagnosis.

Endomyocardial biopsy

In the cardiac presentation, endomyocardial biopsy demonstrates abnormal cardiac glycogen storage.

Show evidence (1 reference)

PMID:31628455 SUPPORT Human Clinical

"material (arrow) in the central part of each cardiomyocyte, corresponding to glycogen and polyglucosan"

Endomyocardial biopsy demonstrates abnormal glycogen and polyglucosan accumulation in cardiomyocytes.

{ }

Source YAML

click to show

name: GYG1-Related Disorder of Glycogen Metabolism
creation_date: "2026-10-04T12:30:00Z"
category: Mendelian
synonyms:
- glycogenin-1 deficiency
- GYG1 deficiency
- glycogen storage disease XV
- polyglucosan body myopathy type 2
disease_term:
  preferred_term: GYG1-related disorder of glycogen metabolism
  term:
    id: MONDO:0100314
    label: GYG1-related disorder of glycogen metabolism
notes: >-
  A single gene-defined entity spanning two named presentations of biallelic
  GYG1 (glycogenin-1) deficiency: glycogen storage disease XV (OMIM 613507),
  with cardiomyopathy, and polyglucosan body myopathy type 2 (OMIM 616199),
  a skeletal myopathy. Which pole predominates depends on the variant: absent
  (truncating) glycogenin-1 gives a skeletal myopathy with glycogen and
  polyglucosan storage, while a nonfunctional (missense) glycogenin-1 expressed
  in the heart is deleterious and drives cardiomyopathy. No GeneReviews chapter
  exists for GYG1 (checked offline and against a live PubMed [book] search).
has_subtypes:
- name: GSD XV
  display_name: Glycogen storage disease XV (cardiac presentation)
  description: >-
    Presentation dominated by cardiomyopathy and arrhythmia, associated with
    expression of a nonfunctional glycogenin-1 in the heart and storage of
    abnormal glycogen; skeletal muscle may show glycogen depletion.
  subtype_term:
    preferred_term: glycogen storage disease XV
    term:
      id: MONDO:0013291
      label: glycogen storage disease XV
- name: PGBM2
  display_name: Polyglucosan body myopathy type 2 (skeletal presentation)
  description: >-
    Adult-onset, slowly progressive limb-girdle skeletal myopathy with
    accumulation of glycogen and polyglucosan in muscle fibers, typically
    without cardiomyopathy.
  subtype_term:
    preferred_term: polyglucosan body myopathy type 2
    term:
      id: MONDO:0014526
      label: polyglucosan body myopathy type 2
description: >-
  GYG1-related disorder of glycogen metabolism is an autosomal recessive
  condition caused by biallelic loss-of-function variants in GYG1, which encodes
  glycogenin-1, the self-glucosylating protein that primes glycogen synthesis in
  skeletal and cardiac muscle. Loss of normal glycogenin-1 autoglucosylation
  disrupts glycogen synthesis; depending on the variant, affected muscle
  accumulates abnormal, poorly branched glycogen (polyglucosan) or is depleted
  of glycogen. The disorder spans two poles: a skeletal myopathy with
  polyglucosan storage (polyglucosan body myopathy type 2) and a cardiomyopathy
  driven by a deleterious mutant glycogenin-1 in the heart (glycogen storage
  disease XV).
inheritance:
- name: Autosomal recessive inheritance
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  description: Caused by biallelic loss-of-function variants in GYG1 (glycogenin-1).
genetic:
- name: GYG1
  gene_term:
    preferred_term: GYG1
    term:
      id: hgnc:4699
      label: GYG1
  relationship_type: CAUSATIVE
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Glycogen storage disease type XV/polyglucosan body myopathy 2 (OMIM#613507/#616199) is caused by biallelic mutations in the GYG1 gene."
    explanation: Establishes biallelic GYG1 variants as the cause of both named presentations.
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sequencing of the glycogenin-1 gene, GYG1, revealed a nonsense mutation in one allele and a missense mutation, Thr83Met, in the other."
    explanation: Documents biallelic GYG1 variants in the index patient, consistent with recessive inheritance.
pathophysiology:
- name: GYG1 Loss of Function
  role: trigger
  biological_scale: MOLECULAR
  description: >-
    Biallelic GYG1 variants either abolish glycogenin-1 (truncating alleles) or
    yield a nonfunctional protein (missense alleles).
  downstream:
  - target: Impaired Glycogenin-1 Autoglucosylation
    description: Absent or nonfunctional glycogenin-1 cannot prime glycogen synthesis normally.
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Patients with GYG1 mutations are characterized by either the absence of glycogenin-1 or the expression of nonfunctional glycogenin-1, and there is storage of glycogen and polyglucosan in the affected tissues."
    explanation: States the two molecular consequences of GYG1 variants.
- name: Impaired Glycogenin-1 Autoglucosylation
  role: central_effector
  biological_scale: MOLECULAR
  description: >-
    Glycogenin-1 normally autoglucosylates to build the short oligosaccharide
    primer that glycogen synthase and branching enzyme extend into glycogen.
    Loss of this priming activity disrupts normal glycogen synthesis in muscle.
  molecular_functions:
  - preferred_term: glycogenin glucosyltransferase activity
    modifier: DECREASED
    term:
      id: GO:0008466
      label: glycogenin glucosyltransferase activity
  genes:
  - preferred_term: GYG1
    term:
      id: hgnc:4699
      label: GYG1
  downstream:
  - target: Polyglucosan and Glycogen Accumulation in Skeletal Muscle
    description: In skeletal muscle, loss of glycogenin-1 leads to focal storage of glycogen and polyglucosan.
  - target: Skeletal Muscle Glycogen Depletion
    description: In the founding case, inactivated priming instead depleted glycogen in skeletal muscle.
  - target: Mutant Glycogenin-1 Cardiotoxicity
    description: A nonfunctional glycogenin-1 expressed in the heart is deleterious and stores abnormal glycogen.
  evidence:
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The missense mutation resulted in inactivation of the autoglucosylation of glycogenin-1 that is necessary for the priming of glycogen synthesis in muscle."
    explanation: Identifies loss of glycogenin-1 autoglucosylation as the molecular lesion.
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Glycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2."
    explanation: Clarifies that glycogen synthesis is not abolished without glycogenin-1 and is not rescued by glycogenin-2, so the lesion is abnormal rather than absent synthesis.
- name: Polyglucosan and Glycogen Accumulation in Skeletal Muscle
  role: effector
  biological_scale: TISSUE
  description: >-
    In skeletal muscle, absent glycogenin-1 leads to focal accumulation of
    glycogen and abnormal, poorly branched polyglucosan in muscle fibers.
  cell_types:
  - preferred_term: skeletal muscle fiber
    term:
      id: CL:0008002
      label: skeletal muscle fiber
  locations:
  - preferred_term: skeletal muscle tissue
    term:
      id: UBERON:0001134
      label: skeletal muscle tissue
  chemical_entities:
  - preferred_term: glycogen
    modifier: INCREASED
    term:
      id: CHEBI:28087
      label: glycogen
  downstream:
  - target: Skeletal myopathy
    description: Polyglucosan and glycogen deposits disrupt muscle fibers, causing progressive weakness.
  - target: Limb-girdle muscle weakness
    description: The myopathy manifests as progressive limb-girdle weakness.
  - target: Exercise intolerance
    description: Exercise intolerance is reported in the polyglucosan myopathy.
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers."
    explanation: Supports skeletal-muscle storage of glycogen and polyglucosan as the consequence of glycogenin-1 absence.
- name: Skeletal Muscle Glycogen Depletion
  role: effector
  biological_scale: TISSUE
  description: >-
    In the cardiac/missense pole (the founding GSD XV case), inactivated
    glycogenin-1 priming instead depletes glycogen in skeletal muscle, with a
    shift toward slow-twitch oxidative fibers.
  cell_types:
  - preferred_term: skeletal muscle fiber
    term:
      id: CL:0008002
      label: skeletal muscle fiber
  locations:
  - preferred_term: skeletal muscle tissue
    term:
      id: UBERON:0001134
      label: skeletal muscle tissue
  chemical_entities:
  - preferred_term: glycogen
    modifier: DECREASED
    term:
      id: CHEBI:28087
      label: glycogen
  downstream:
  - target: Muscle weakness
    description: Muscle weakness accompanies the skeletal glycogen depletion in this pole.
  - target: Type 1 muscle fiber predominance
    description: The depleted muscle shows a shift toward slow-twitch oxidative fibers.
  evidence:
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "muscle weakness, associated with the depletion of glycogen in skeletal muscle"
    explanation: Documents skeletal-muscle glycogen depletion in the founding case, the pole opposite to polyglucosan storage.
- name: Mutant Glycogenin-1 Cardiotoxicity
  role: effector
  biological_scale: TISSUE
  description: >-
    When a nonfunctional (missense) glycogenin-1 is expressed in the heart it is
    deleterious, with storage of abnormal glycogen and cardiomyopathy. Whether the
    mutant protein is itself sufficient to cause the cardiomyopathy is unresolved,
    since patients who completely lack glycogenin-1 do not develop it (see discussions).
  cell_types:
  - preferred_term: cardiac muscle cell
    term:
      id: CL:0000746
      label: cardiac muscle cell
  locations:
  - preferred_term: cardiac muscle tissue
    term:
      id: UBERON:0001133
      label: cardiac muscle tissue
  downstream:
  - target: Cardiomyopathy
    description: Storage of abnormal glycogen in cardiomyocytes produces cardiomyopathy.
  - target: Arrhythmia
    description: Abnormal cardiac storage material is associated with conduction disturbance.
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy."
    explanation: Supports a deleterious mutant glycogenin-1 in the heart as the driver of cardiomyopathy.
phenotypes:
- name: Skeletal myopathy
  subtype: PGBM2
  description: >-
    Adult-onset, slowly progressive skeletal muscle disease with limb-girdle
    weakness and polyglucosan storage on biopsy.
  phenotype_term:
    preferred_term: Skeletal myopathy
    term:
      id: HP:0003198
      label: Myopathy
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Most of these patients had adult-onset, slowly progressive myopathy and muscle weakness without cardiomyopathy"
    explanation: Supports the dominant adult-onset skeletal myopathy presentation.
- name: Limb-girdle muscle weakness
  subtype: PGBM2
  description: Progressive limb-girdle weakness, typically presenting in mid to late adulthood.
  phenotype_term:
    preferred_term: Limb-girdle muscle weakness
    term:
      id: HP:0003325
      label: Limb-girdle muscle weakness
  evidence:
  - reference: PMID:26652229
    reference_title: Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five Sardinian patients presented in their 5th or 6th decade with progressive limb girdle muscle weakness"
    explanation: Documents late-onset progressive limb-girdle weakness in a GYG1 cohort.
- name: Exercise intolerance
  subtype: PGBM2
  description: Reduced capacity for exertion, a recognized feature of GYG1-related polyglucosan body myopathy.
  phenotype_term:
    preferred_term: Exercise intolerance
    term:
      id: HP:0003546
      label: Exercise intolerance
  evidence:
  - reference: PMID:26652229
    reference_title: Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Exercise intolerance is a relatively new clinical finding of GYG1-related polyglucosan body myopathy"
    explanation: Documents exercise intolerance as a feature of the polyglucosan myopathy.
- name: Muscle weakness
  subtype: GSD XV
  description: Skeletal muscle weakness in the glycogen-depletion (cardiac/missense) pole.
  phenotype_term:
    preferred_term: Muscle weakness
    term:
      id: HP:0001324
      label: Muscle weakness
  evidence:
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "muscle weakness, associated with the depletion of glycogen in skeletal muscle"
    explanation: Documents muscle weakness with skeletal glycogen depletion in the founding case.
- name: Type 1 muscle fiber predominance
  subtype: GSD XV
  description: A shift toward slow-twitch oxidative fibers on muscle biopsy in the glycogen-depletion pole.
  phenotype_term:
    preferred_term: Type 1 muscle fiber predominance
    term:
      id: HP:0003803
      label: Type 1 muscle fiber predominance
  evidence:
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The skeletal muscle showed a marked predominance of slow-twitch, oxidative muscle fibers and mitochondrial proliferation."
    explanation: Documents the slow-twitch oxidative fiber predominance in the founding case.
- name: Cardiomyopathy
  subtype: GSD XV
  description: Cardiomyopathy from storage of abnormal glycogen in cardiomyocytes, which can progress to heart failure.
  phenotype_term:
    preferred_term: Cardiomyopathy
    term:
      id: HP:0001638
      label: Cardiomyopathy
  sequelae:
  - target: Congestive heart failure
    description: Progressive cardiomyopathy can decompensate into congestive heart failure.
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy."
    explanation: Supports cardiomyopathy as a consequence of mutant glycogenin-1 in the heart.
- name: Arrhythmia
  subtype: GSD XV
  description: Cardiac arrhythmia associated with abnormal storage material in the heart.
  phenotype_term:
    preferred_term: Arrhythmia
    term:
      id: HP:0011675
      label: Arrhythmia
  evidence:
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "cardiac arrhythmia, associated with the accumulation of abnormal storage material in the heart"
    explanation: Documents arrhythmia with abnormal cardiac storage in the index patient.
- name: Congestive heart failure
  subtype: GSD XV
  description: Progressive cardiac dysfunction decompensating to heart failure, in some cases requiring transplantation.
  phenotype_term:
    preferred_term: Congestive heart failure
    term:
      id: HP:0001635
      label: Congestive heart failure
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cardiac failure with reduced ejection fraction. Cardiac arrhythmias."
    explanation: Documents cardiac failure with reduced ejection fraction in a GYG1 cardiomyopathy patient.
histopathology:
- name: Polyglucosan bodies in muscle
  description: >-
    Subsarcolemmal and intermyofibrillar deposits that are PAS-positive and
    partially diastase (alpha-amylase) resistant, consistent with polyglucosan.
  evidence:
  - reference: PMID:26652229
    reference_title: Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "PAS-positive deposits consistent with polyglucosan"
    explanation: Describes the diagnostic polyglucosan deposits on muscle biopsy.
diagnosis:
- name: Muscle biopsy
  description: >-
    Muscle biopsy showing PAS-positive, diastase-resistant polyglucosan deposits
    (storage pole) or glycogen depletion (depletion pole).
  evidence:
  - reference: PMID:26652229
    reference_title: Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "PAS-positive deposits consistent with polyglucosan"
    explanation: Muscle-biopsy polyglucosan deposits are the histological basis of diagnosis.
- name: Glycogenin-1 protein testing
  description: >-
    Western blot or immunohistochemistry showing absent or unglucosylated
    glycogenin-1 in muscle and heart.
  evidence:
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Western blotting showed the presence of unglucosylated glycogenin-1 in the muscle and heart."
    explanation: Protein-level demonstration of unglucosylated glycogenin-1 supports the diagnosis.
- name: GYG1 molecular testing
  description: Sequencing of GYG1 to identify biallelic pathogenic variants confirms the diagnosis.
  evidence:
  - reference: PMID:20357282
    reference_title: Glycogenin-1 deficiency and inactivated priming of glycogen synthesis.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Sequencing of the glycogenin-1 gene, GYG1, revealed a nonsense mutation in one allele and a missense mutation, Thr83Met, in the other."
    explanation: Biallelic GYG1 variants on sequencing establish the molecular diagnosis.
- name: Endomyocardial biopsy
  description: In the cardiac presentation, endomyocardial biopsy demonstrates abnormal cardiac glycogen storage.
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "material (arrow) in the central part of each cardiomyocyte, corresponding to glycogen and polyglucosan"
    explanation: Endomyocardial biopsy demonstrates abnormal glycogen and polyglucosan accumulation in cardiomyocytes.
treatments:
- name: Supportive care
  description: >-
    Management is symptomatic: surveillance and treatment of cardiomyopathy and
    arrhythmia, and management of progressive muscle weakness.
  treatment_term:
    preferred_term: Supportive Care
    term:
      id: NCIT:C15747
      label: Supportive Care
- name: Cardiac transplantation
  description: Heart transplantation for advanced, decompensated cardiomyopathy.
  treatment_term:
    preferred_term: Heart Transplantation
    term:
      id: NCIT:C15246
      label: Heart Transplantation
  target_mechanisms:
  - target: Congestive heart failure
    description: Transplantation replaces the failing heart in end-stage cardiac disease.
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cardiac failure. Heart transplantation at age 48"
    explanation: Documents heart transplantation for cardiac failure in a GYG1 patient.
discussions:
- discussion_id: mutant_glycogenin1_cardiomyopathy_causation
  kind: KNOWLEDGE_GAP
  prompt: >-
    Does expression of a mutant glycogenin-1 in the heart actually cause the
    cardiomyopathy, or is it only associated with it?
  attaches_to:
  - pathophysiology#Mutant Glycogenin-1 Cardiotoxicity
  rationale: >-
    The cardiac phenotype tracks with expression of a nonfunctional glycogenin-1
    rather than with loss of glycogenin-1 as such: patients who completely lack
    the protein from biallelic truncating variants do not develop cardiomyopathy.
    Whether the mutant protein is itself sufficient to cause the cardiomyopathy is
    not settled.
  evidence:
  - reference: PMID:31628455
    reference_title: "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "An important question is whether expression of mutated glycogenin-1 does in fact cause cardiomyopathy since patients who completely lack glycogenin-1 because of biallelic truncating GYG1 mutations do not develop cardiomyopathy"
    explanation: The source explicitly leaves cardiomyopathy causation open and distinguishes truncating from missense alleles.
- discussion_id: why_polyglucosan_forms
  kind: KNOWLEDGE_GAP
  prompt: >-
    Why does loss of glycogenin-1 lead to accumulation of abnormal, poorly
    branched polyglucosan rather than simply less glycogen?
  attaches_to:
  - pathophysiology#Polyglucosan and Glycogen Accumulation in Skeletal Muscle
  rationale: >-
    Glycogen is still synthesized without glycogenin-1, but the product is
    abnormal. An imbalance between glycogen synthase and branching enzyme
    activity has been proposed, but the mechanism linking loss of priming to
    polyglucosan is not established.
  evidence:
  - reference: PMID:26652229
    reference_title: Late-onset polyglucosan body myopathy in five patients with a homozygous mutation in GYG1.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the cause of polyglucosan accumulation remains difficult to understand"
    explanation: The source states directly that the basis of polyglucosan accumulation is unresolved.
datasets: []

📚

References & Deep Research

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: GYG1-Related Disorder of Glycogen Metabolism · 2026-10-04T12:43:39Z · View source

New gene-defined Mendelian entry for biallelic GYG1 (glycogenin-1) deficiency, MONDO:0100314, curated de novo from the stubs/ queue (stub deleted in this PR; unclaimed). Deep research via claude_code (lead-only; term validation 16/16, 3 benign paraphrases). Modeled as one entity with two has_subtypes: GSD XV (MONDO:0013291, cardiac) and polyglucosan body myopathy type 2 (MONDO:0014526, skeletal). Causal chain: GYG1 LOF -> impaired glycogenin-1 autoglucosylation (loss of glycogen priming) -> branch: (a) absent glycogenin-1 -> focal glycogen/polyglucosan accumulation in skeletal muscle -> skeletal myopathy + proximal weakness (PGBM2); (b) nonfunctional mutant glycogenin-1 in heart -> abnormal glycogen storage -> cardiomyopathy + arrhythmia (GSD XV). 4/4 phenotypes causally connected; phenotypes stratified by subtype FK. Histopathology: PAS-positive, diastase-resistant polyglucosan on muscle biopsy. Evidence anchored on Moslemi 2010 NEJM (PMID:20357282, index case, autoglucosylation inactivation), Visuttijai 2020 JCEM (PMID:31628455, full text, skeletal-vs-cardiac mechanism + biallelic nosology) and Akman 2015 (PMID:26652229, five-patient Sardinian polyglucosan cohort). No GeneReviews chapter (checked offline + live PubMed [book]). 11/11 snippets verified; all terms valid; full gate suite green. Avoided quoting Akman's alpha-amylase phrase because the Greek alpha does not fold in snippet normalization.

Claude Code ▸

GYG1-Related Disorder of Glycogen Metabolism (Glycogen Storage Disease XV, glycogenin-1 deficiency): research report

claude-haiku-4-5-20251001, claude-sonnet-5-5 8 citations 2026-10-04T12:36:44.799968

GYG1-Related Disorder of Glycogen Metabolism (Glycogen Storage Disease XV, glycogenin-1 deficiency): research report

Method and limits. I ran three web searches only, so this is not an exhaustive review. Items marked [verified] were seen in those results. Items marked [unverified] come from my background knowledge. Check those, especially PMIDs, MONDO and HPO IDs, and all numeric frequencies, with just fetch-reference and just validate-terms before using them in the KB. Per the repo rules, none of the CURIEs below were looked up in a cache, so treat them as leads and not as bindings.

Searches that returned too little or nothing. Prevalence and incidence, newborn screening, treatment trials and NCT numbers, and OMIA/VBO veterinary data were not searched. Population-specific data, such as the Sardinian cluster, rest on one search snippet.

1. Disease information

Overview [verified]. Glycogenin-1 deficiency is a rare glycogen storage disorder. Biallelic (homozygous or compound heterozygous) deleterious variants in GYG1 cause either a slowly progressive adult-onset myopathy with polyglucosan storage in muscle fibres, or a cardiomyopathy with little or no skeletal muscle weakness. (Hedberg-Oldfors review/cohort, PMC7046021; PubMed 31628455)
Identifiers.
Gene OMIM 603942 (GYG1) [verified]. The OMIM disease entry is "Glycogen storage disease XV" (GSD15); I recall 613507 for the disease entry [unverified].
MONDO:0100314 is as given in the template and was not checked. KEGG Medicus H01955 appeared in results [verified].
Orphanet, ICD-10 (E74.0x) and MeSH IDs were not retrieved.
Synonyms.
Glycogenin-1 deficiency.
GSD XV / GSD15.
Polyglucosan body myopathy type 2 (PGBM2) [unverified].
Muscle glycogen storage disease associated with glycogenin-1 deficiency.
Data provenance. The literature is case reports and small cohorts of individual patients. Disease-level resources such as OMIM and Orphanet aggregate these reports. No EHR-derived source was found.

2. Etiology

Cause. Biallelic loss-of-function or hypomorphic GYG1 variants. Variants that are compatible with expressed protein can nonetheless be harmful, as the p.Asp102His cardiac cases show (see section 4).
Genetic risk factors. Biallelic GYG1 variants are the only established cause. No modifier genes were identified in the sources I saw.
Environmental and protective factors, gene-environment interactions. None known.

3. Phenotypes

Phenotype	Suggested HPO (to verify)	Notes
Proximal/limb-girdle muscle weakness	HP:0003701 (Proximal muscle weakness)	Slowly progressive, adult onset (5th–6th decade in the Sardinian patients) [verified]
Vacuolar myopathy with PAS-positive polyglucosan deposits	HP:0003803 (Type 1 muscle fibre predominance) and HP:0003713 (muscle fibre necrosis) are not the right terms. Look up a polyglucosan or glycogen-storage-in-muscle term instead.	Subsarcolemmal and intermyofibrillar vacuoles, partly α-amylase-resistant [verified]
Cardiomyopathy	HP:0001638 (Cardiomyopathy)	Seen in the p.Asp102His men aged 34–52 [verified]. Can present with severe cardiac failure and little or no skeletal muscle weakness
Cardiac arrhythmia	HP:0011675 (Arrhythmia)	In the first reported patient (Moslemi 2010) [verified]
Exercise intolerance / myalgia	HP:0003546	Reported in some patients [unverified]

Frequency and severity. Frequencies per phenotype were not retrieved. Do not assign percentages without a source.
Quality of life. No data found.

4. Genetic and molecular information

Gene. GYG1 (glycogenin-1; HGNC ID not looked up, so verify against cache/hgnc before using the lowercase hgnc: form).
Index case. Moslemi et al. described a 27-year-old man with muscle weakness and cardiac arrhythmia who was compound heterozygous for a nonsense variant and the missense variant p.Thr83Met. The missense variant abolished glycogenin-1 autoglucosylation, which primes glycogen synthesis (N Engl J Med 2010, PMID:20357282) [verified].
Cohort. Malfatti and colleagues (Ann Neurol 2014, PMID not confirmed) described 7 unrelated adults with homozygous or compound heterozygous deleterious variants [verified]. Most had no detectable glycogenin-1 in muscle. One had a protein lacking the C-terminus, which normally binds glycogen synthase. The authors concluded that either depletion of glycogenin-1 or impaired interaction with glycogen synthase underlies the disease.
Cardiac variant. Three unrelated men with cardiomyopathy were homozygous for p.Asp102His. The mutant protein expressed in heart had lost autoglucosylation (Hedberg-Oldfors et al., PMC4724519 is a likely source; confirm) [verified for the finding; unverified for the citation].
Variant class. Nonsense, missense, splice and null alleles. Functional consequence is loss of function, or loss of autoglucosylation or glycogen synthase binding.
Epigenetic and chromosomal data. None.

5. Environmental information

No environmental, lifestyle or infectious factors are known.

6. Mechanism and pathophysiology

Causal chain

Biallelic GYG1 variants lead to absent, truncated or catalytically inactive glycogenin-1.
Without functional glycogenin-1, the autoglucosylation (self-priming) step of glycogen synthesis is lost. This is demonstrated for p.Thr83Met and p.Asp102His in vitro.
Branch point A, skeletal muscle with glycogenin-1 absent: muscle can still make glycogen, because glycogenin-2 or other priming routes compensate. This is inferred from the finding that glycogen synthesis proceeds without glycogenin (PubMed 31628455, "dispensable for glycogen synthesis in human muscle"). The result is focal accumulation of glycogen and polyglucosan, vacuolar myopathy and progressive weakness.
Branch point B, heart with a mutant protein that is expressed but inactive: abnormal glycogen is stored, which leads to cardiomyopathy. The proposed explanation is that the expressed mutant protein is deleterious in cardiac tissue, whereas complete absence is better tolerated [verified in the search summary; mechanism is the authors' interpretation].
Polyglucosan storage disrupts myofibre architecture and cardiac contractility, leading to the clinical phenotype. This step is inferred.

Suggested terms (to verify) - GO: glycogen biosynthetic process (GO:0005978), glycogenin glucosyltransferase activity (GO:0008466), glycogen metabolic process (GO:0005977). - CL: skeletal muscle fibre (CL:0008002), cardiac muscle cell (CL:0000746). - UBERON: skeletal muscle tissue, heart. - Subcellular: sarcoplasm, subsarcolemmal and intermyofibrillar regions. - Molecular profiling, advanced technologies and immune involvement: nothing found.

7. Anatomical structures affected

Primary: skeletal muscle, mainly proximal and limb-girdle, and heart.
Tissue: muscle fibres with vacuoles containing polyglucosan.
Laterality: presumably bilateral and symmetric. This was not documented in the sources I saw.

8. Temporal development

Onset: mostly adult onset (5th–6th decade in the Sardinian patients), but cardiac presentations occurred in the 3rd to 6th decade (ages 34–52 in the p.Asp102His men) [verified].
Progression: slowly progressive myopathy. Cardiac course is variable and can reach severe heart failure [verified].

9. Inheritance and population

Inheritance: autosomal recessive.
Founder effects: a cluster of five Sardinian patients was reported [verified; variant not retrieved]. The p.Asp102His recurrence in unrelated men suggests a recurrent or founder allele [inferred].
Prevalence, incidence, carrier frequency, sex ratio: not found.

10. Diagnostics

Muscle biopsy: vacuoles with PAS-positive, partly diastase-resistant polyglucosan. Immunohistochemistry or Western blot shows absent or reduced glycogenin-1 in most patients [verified].
Genetic testing: GYG1 sequencing, or a neuromuscular or cardiomyopathy gene panel or exome.
Other tests: CK, EMG, cardiac MRI, echocardiography and ECG are reasonable. I did not retrieve specific findings.
Differential diagnosis: other polyglucosan storage diseases (GBE1-related disease, Pompe disease and other glycogenoses).
Screening: none established.

11. Outcome and prognosis

Not retrieved. Prognosis is driven by cardiac involvement, which can cause severe cardiac failure [verified]. No survival data found.

12. Treatment

No disease-specific therapy found. Management is supportive: cardiac surveillance and standard heart-failure or arrhythmia care, and physical therapy. No clinical trials were identified, and I did not search ClinicalTrials.gov. Suggested NCIT terms (verify): Supportive Care (NCIT:C15747), Physical Therapy (NCIT:C15302), Pharmacotherapy (NCIT:C15986).

13. Prevention

Genetic counselling for autosomal recessive risk (NCIT:C15240). Cascade testing of relatives and cardiac surveillance of carriers of cardiomyopathy-associated genotypes are reasonable but unsourced here.

14. Other species and natural disease

Not searched. OMIA and VBO have not been checked.

15. Model organisms

Mouse: a constitutive Gyg knockout (gene-trap) mouse has been reported [verified in search summary; the primary citation was not seen]. About 90% of embryos were lost, but survivors still synthesised glycogen and accumulated high levels of it, especially in skeletal and cardiac muscle. This parallels the human finding that glycogen synthesis continues without glycogenin-1.
Limits: the high lethality and the glycogen accumulation phenotype are not clearly the same as the adult human myopathy. Other models were not searched.
Evidence-source tagging: the mouse work should be tagged MODEL_ORGANISM, and the human biopsy and genetic data HUMAN_CLINICAL.

Priority follow-ups before curation

Fetch and quote the primary papers: PMID:20357282 (Moslemi 2010), the Malfatti 2014 Ann Neurol paper (find its PMID), PMID:31628455, PMC4724519 and PMC7046021.
Check for a GeneReviews chapter with just check-genereviews, and check ClinGen validity with just list-gene-validity.
Search for Orphanet prevalence and the HPO annotations for GSD XV.
Verify every HPO, GO and CL CURIE above, and replace the phenotype row where I did not give a confident term.

Sources: - PubMed 31628455 - PMC7046021 - PMC4724519 - OMIM *603942 mirror - Institut de Myologie - Reactome R-HSA-3814838 - Malfatti cohort and mouse model (UB repository)

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

Outcome	Count
References checked	4
Resolved	4
Unresolved (possible confabulation)	0
Unverifiable	0
References weighed for topical relevance	4
On topic	4
Off topic	0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome	Count
Terms checked	16
Resolved	16
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	0
Terms whose name was checked	6
Terms named correctly	3
Terms named as a different term	0
Terms whose name is worth a second look	3

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

HP:0003546 (1 mention) - the report calls it "Exercise intolerance / myalgia"; HP calls it Exercise intolerance
GO:0005978 (1 mention) - the report calls it "GO: glycogen biosynthetic process"; GO calls it glycogen biosynthetic process
CL:0008002 (1 mention) - the report calls it "CL: skeletal muscle fibre"; CL calls it skeletal muscle fiber

Every term resolved, and every label the report gave matched.

GYG1-Related Disorder of Glycogen Metabolism

Ask OpenScientist

OpenScientist Report

Inheritance

Subtypes

Discussions and Knowledge Gaps

Pathophysiology

Histopathology

Pathograph

Phenotypes

Genetic Associations

Medical Actions

Diagnosis

Source YAML

References & Deep Research

Deep Research

GYG1-Related Disorder of Glycogen Metabolism (Glycogen Storage Disease XV, glycogenin-1 deficiency): research report

1. Disease information

2. Etiology

3. Phenotypes

4. Genetic and molecular information

5. Environmental information

6. Mechanism and pathophysiology

7. Anatomical structures affected

8. Temporal development

9. Inheritance and population

10. Diagnostics

11. Outcome and prognosis

12. Treatment

13. Prevention

14. Other species and natural disease

15. Model organisms

Priority follow-ups before curation

Reference Validation

Term Validation

Terms whose name is worth a second look