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Canine Mendelian disease record

Glycogen Storage Disease, Type Ia (GSD Ia)

Glycogen Storage Disease, Type Ia (GSD Ia). Autosomal recessive. Observed in 2 of 266 breeds tested in the Sniff Atlas, with measured carrier frequencies drawn from 242,665 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:000418-9615
Autosomal recessive
Source dataset
Sniff Atlas v1.0.1 / DOI
The human connection

A model of human glycogen storage disease due to glucose-6-phosphatase deficiency type IA

This is the canine counterpart of glycogen storage disease due to glucose-6-phosphatase deficiency type IA 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: Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type a, or glycogen storage disease (GSD) type 1a, is a type of glycogenosis due to G6P deficiency.

In humans it is also called: GSD1, GSD1A, G6P deficiency type 1a, G6PC glycogen storage disease, glycogen storage disease 1A.

MONDO:0009287 OMIM 232200

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 I is a severe disorder of glycogen metabolism characterized by glycogen accumulation, particularly in the liver. Signs include severe hepatomegaly, failure to thrive, coma, and death. There is a genetic test available.

Clinical features

Affected animals are hypoglycemic if fasted, and develop lactic acidosis, hypertriglyceridemia, and hyperuricemia (Specht et al., 2011). Signs include severe hepatomegaly, poor body condition, lethargy, failure to thrive, coma, and death.

Molecular genetics

By cloning and sequencing a very likely comparative candidate gene (based on the homologous human disorder), Kishnani et al. (1997) showed that the causative mutation in [Maltese Terrier] dogs is a G to C transversion in the G6PC (glucose-6-phosphatase) gene that changes the amino acid codon from methionine to isoleucine (M121I), producing a variant of the enzyme with "15 times less enzyme activity". Christen et al. (2021) conducted whole genome sequencing in one of two affected purebred German Pinscher puppies and "revealed a homozygous 76 bp insertion into exon 5 of the G6PC1 candidate gene, which probably causes a loss of function (chr9:g.20,134,857_20,134,858ins76; XM_038676372.1:c.634_635ins76). The insertion consisted of 60 consecutive adenines and an additional 16 bp duplication of the integration site ... ."

Pathology

Glucose-6-phosphate catalyzes the production of glucose from glucose-6-phosphate. The mutant G6PC has 15 times less activity than the normal enzyme (Kishnani et al., 1997) and decreased amounts in the liver and kidney (Kishnani et al., 2001). Affected dogs develop severe hypoglycemia, glycogen storage, and progressive hepatomegaly. Hepatocytes are diffusely vacuolated, containing large quantities of glycogen. Soft tissue mineralization can occur in renal tubules and pulmonary alveolar septa (Brix et al., 1995).

Prevalence

Christen et al. (2021) genotyped 208 German Pinscher dogs for the German Pinscher variant and identified a carrier frequency of 12%.

Control

Parents and siblings of affected dogs should be tested. Mating that could result in affected dogs should be avoided. Arnson et al. (2023) "attempted genome editing ... in a dog model for GSD Ia. We demonstrated donor transgene integration in the liver of three adult-treated dogs accompanied by stable G6Pase expression and correction of hypoglycemia during fasting. Two puppies with GSD Ia were treated by genome editing that achieved donor transgene integration in the liver. Integration frequency ranged from 0.5% to 1% for all dogs. ... Thus, genome editing can integrate a therapeutic transgene in the liver of a large animal model, either early or later in life, and further development is warranted to provide a more stable treatment for GSD Ia." (This study involves genetically modified organisms (GMO).

Genetic testing

The base substitution in Maltese Terriers removes an NcoI restriction site, thereby enabling a simple RFLP PCR test to detect carriers.

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 232200 Gene · OMIM 613742

Source: OMIA (Nicholas, Tammen & the Sydney Informatics Hub), entry OMIA:000418-9615, 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 due to glucose-6-phosphatase deficiency type IA (MONDO:0009287).

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 20.

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 Ia (GSD Ia) 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 Ia (GSD Ia) looks like in your dog's breed.
Carrier frequency by breed

Top 2 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%1%2%
Maltese0.33% · n 2,413
Yorkshire Terrier<0.1% · n 8,367
n = 10,780 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 Ia (GSD Ia) is measured; phenotype outcome depends on penetrance and modifiers.
▸ Full table with Wilson 95% confidence intervals
Breed Carrier frequency n tested
Maltese 0.33% 2,413
Yorkshire Terrier <0.1% 8,367

264 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:000418-9615.

  • 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:000418-9615 · Donner et al. 2023