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Canine Mendelian disease record

Glycogen Storage Disease, Type IIIa (GSD IIIa)

Glycogen Storage Disease, Type IIIa (GSD IIIa). Autosomal recessive. Observed in 1 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,659 dogs (Donner 2023). Per-dog phenotype outcome depends on penetrance, modifiers, and environment; the carrier frequencies below describe variant prevalence, not disease incidence.

OMIA identifier
OMIA:001577-9615
Autosomal recessive
Pathogenic
Source dataset
Sniff Atlas v1.0.1 / DOI

The Pathogenic grade describes the documented variant's causality, per the Animal Variant Classification Guidelines (AVCG; Boeykens et al. 2024, Front Vet Sci), an ACMG/AMP-style framework curated in OMIA. It grades the variant, not any individual dog. See the full classification table.

The human connection

A model of human glycogen storage disease III

This is the canine counterpart of glycogen storage disease III in people. That makes affected dogs a naturally-occurring model of the human disease, and it is part of why studying dogs moves medicine forward for everyone. It does not mean your dog has the human disease. It means the two share an underlying biology.

In people, the disease is described as: Glycogen debranching enzyme (GDE) deficiency, or glycogen storage disease type 3 (GSD 3), is a form of glycogen storage disease characterized by severe muscle weakness and hepatopathy.

In humans it is also called: GSD3, GSDIII, AGL glycogen storage disease, amylo-1,6-glucosidase deficiency, Cori disease.

MONDO:0009291 OMIM 232400

Mapped from OMIA via the human disease's OMIM entry to the Mondo Disease Ontology (Monarch Initiative, CC-BY 4.0). Sniff renders this as a model-of link; the canine disease remains the subject of this page.

About this disease

From OMIA's curated record

Documented in OMIA (Online Mendelian Inheritance in Animals). This describes the disease as recorded in the published literature, not a prediction for any individual dog. As of 2026-06-03.

Summary

Glycogen storage disease IIIa (GSD IIIa) is a disorder of glycogen metabolism characterized by glycogen accumulation in tissue and altered glucose homeostasis. Lethargy, exercise intolerance, and collapse after exercise may become apparent by 14 months of age. Dogs with GSD IIIa are deficient in glycogen debranching enzyme, so instead of breaking down glycogen into glucose, they accumulate abnormal glycogen particles. This mostly happens in liver and muscle, which are the tissues that have the highest levels of glycogen metabolism. The mode of inheritance is autosomal recessive. The causative mutation is an adenosine deletion causing premature termination of AGL translation. A test is available to detect the mutation. Parents and siblings of affected dogs should be tested. Breeding of affected animals is not recommended. If a carrier must be bred, it is advised to breed that dog only to a dog that has tested as homozygous normal. Edited by John C. Fyfe, D.V.M., Ph.D.

Clinical features

Affected dogs show increases in ALT, ALP, and CK within the first year of life. By 14 months of age, lethargy, exercise intolerance, and collapse after exercise may become apparent (Gregory et al., 2007). The disease in Curly-Coated Retrievers is mild compared to what was reported in German shepherds (Ceh et al., 1976; Rafiquzzaman et al., 1976) as a severe metabolic derangement that led to death or euthanasia by 15 months of age. This is likely due to a different mutation or genetic background. Yi et al. (2012) provided a detailed clinical account of the disorder in Curly Coat Retrievers, having established a colony that segregates for the causal mutation described above. They summarise their findings as: " Abnormally high glycogen deposition was found in liver and muscle, and, consistent with liver and muscle damage, high and gradually increasing activity of enzymes including AST, ALT, ALP and CPK were found in serum. In muscle, increased glycogen deposition was accompanied by disruption of the contractile apparatus and fraying of myofibrils. Progressive, age-related liver fibrosis and muscle damage caused by glycogen accumulation were the major features of GSD IIIa in affected dogs."

Molecular genetics

The causative mutation is an adenosine deletion causing premature termination of AGL translation (Gregory et al., 2007). There is an analogous human condition (OMIM# 232400).

Pathology

In a normal dog, the release of glucagon stimulates the breakdown of glycogen. This breakdown happens through the work of phosphorylase and glycogen debranching enzyme. Dogs with GSD IIIa are deficient in glycogen debranching enzyme, so instead of breaking down glycogen into glucose, they accumulate abnormal glycogen particles. This mostly happens in liver and muscle, which are the tissues that have the highest levels of glycogen metabolism (Gregory et al., 2007). Livers of affected animals are dark red, enlarged, and friable, with smooth edges and a grainy surface appearance. On histologic examination, hepatocytes show global cellular swelling with diaphanous eosinophilic (foamy) cytoplasm, but no evidence of inflammation, fibrosis, or cytoplasmic fat. Glycogen accumulation is evident with PAS staining (Gregory et al., 2007). Glucose homeostasis may be sufficiently affected in times of stress to cause hypoglycemia.

Control

Parents of affected dogs are obligate carriers, and siblings should be tested. Breeding of affected animals is not recommended. If a carrier must be bred, it is advised to breed that dog only to a dog that has tested as homozygous normal.

Genetic testing

A test is available to detect the mutation.

Human analog

OMIA links this condition to its human counterpart in OMIM (Mendelian Inheritance in Man), the place to read across to the deeper human literature for the same biology.

Disease · OMIM 232400 Gene · OMIM 610860

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:001577-9615, doi:10.25910/2AMR-PV70 (CC-BY 4.0).

Signs & cross-references

How it presents

Catalogued in the Mondo disease ontology (the cross-species disease identity used by the Monarch Initiative) as glycogen storage disease III (MONDO:0009291).

Phenotype terms: Human Phenotype Ontology + Mammalian Phenotype Ontology; disease terms: Mondo (Monarch Initiative). Cross-references curated by OMIA (doi:10.25910/2AMR-PV70, CC-BY 4.0).

The evidence

Published references

The peer-reviewed papers behind this disease, curated by OMIA. Starred entries are OMIA-designated landmark papers. Showing 6 of 9.

  5. Glycogen storage disease type IIIa in curly-coated retrievers. · J Vet Intern Med · 2007 · PMID 17338148

References curated by OMIA (Nicholas, Tammen & the Sydney Informatics Hub), doi:10.25910/2AMR-PV70 (CC-BY 4.0). Full list at the OMIA entry.

Predict a litter

Set each parent's status for Glycogen Storage Disease, Type IIIa (GSD IIIa) and see the odds for their puppies. Single recessive variant, exact Mendelian math.

Parent A
Parent B
NNClear
NmCarrier
NmCarrier
mmAffected
Clear25%
Carrier50%
Affected25%

These are the genetic odds for one known variant, not a promise: a real litter varies around them, and penetrance or other genes can change whether the condition ever appears. Use it to avoid pairing two carriers and to keep a line healthy, not to engineer a dog. Inheritance mode per OMIA.
Your breed

See what Glycogen Storage Disease, Type IIIa (GSD IIIa) looks like in your dog's breed.
Carrier frequency by breed

Top 1 well-sampled breeds (n ≥ 50)

Maximum per breed across variants in the Donner 2023 cohort, with . The list below is split into well-sampled breeds (n ≥ 50 tested) and small-sample breeds (n < 50, where the Wilson CI typically spans more than 20 percentage points and frequencies should not be compared directly to the well-sampled entries). Frequencies are population-level, not per-litter or per-line.

0%10%20%
Curly Coated Retriever6.3% · n 63
n = 63 dogs · Donner et al. 2023 carrier-screening cohort · Sniff Atlas
Each bar is one well-sampled breed; the whisker is its Wilson 95% CI, and fainter bars have wider intervals. Frequencies are population-level, not per-litter. Carrier status for Glycogen Storage Disease, Type IIIa (GSD IIIa) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Curly Coated Retriever 6.3% 63

265 additional breeds in the Donner 2023 cohort were tested but showed no carriers.

Scope of this record

Scope

This record carries the breed-level carrier frequencies from the Donner 2023 cohort. Penetrance data (the fraction of at-risk dogs that develop the phenotype) is not yet quantified for this disease in the Sniff Atlas v1.0.1. The OMIA entry is the authoritative reference for the clinical phenotype, inheritance pattern, and gene assignment.

Predicted disease relevance at the per-dog level is UNPROVEN. The carrier frequency is measured; phenotype outcome depends on penetrance, environment, and modifier loci. Consult a veterinarian for clinical interpretation.

How to cite this record

Citations

If you use this record in published work, cite the Sniff Atlas (the published dataset that carries the breed-level carrier frequencies) and the upstream sources:

  • Sniff Atlas v1.0.1 for the per-breed carrier frequencies:

    Gehring, M. (2026). Sniff Atlas v1.0.1. Zenodo. https://doi.org/10.5281/zenodo.20566358. CC-BY 4.0.

  • OMIA for the disease definition, inheritance, and gene assignment:

    Nicholas, F. W., & Tammen, I. (2024). OMIA. Sydney Informatics Hub, The University of Sydney. https://doi.org/10.25910/2AMR-PV70. Entry: OMIA:001577-9615.

  • Donner et al. 2023 for the breed × variant carrier-frequency cohort:

    Donner, J., Freyer, J., Davison, S., Anderson, H., Blades, M., Honkanen, L., et al. (2023). Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs. PLOS Genetics, 19(2), e1010651. https://doi.org/10.1371/journal.pgen.1010651.

Full citation formats (BibTeX, RIS, CITATION.cff) at sniff.world/cite.

Related

Related

Last updated
Sources: Sniff Atlas v1.0.1 · OMIA OMIA:001577-9615 · Donner et al. 2023