OMIA 000418-9615 : Glycogen storage disease Ia in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 232200

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1997

Species-specific description: 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.

Mapping: CFA9

Molecular basis: 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 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".

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.

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).

Control: Parents and siblings of affected dogs should be tested. Carrier should not be bred.

Genetic testing: The base substitution removes an NcoI restriction site, thereby enabling a simple RFLP PCR test to detect carriers.

Breed: Maltese Terriers.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
G6PC glucose-6-phosphatase, catalytic subunit Canis lupus familiaris 9 NC_051813.1 (20862184..20851596) G6PC Homologene, Ensembl, NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Maltese Glycogen storage disease Ia G6PC missense c.450G>C p.M121I 1997 9259982


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2020 Almodóvar-Payá, A., Villarreal-Salazar, M., de Luna, N., Nogales-Gadea, G., Real-Martínez, A., Andreu, A.L., Martín, M.A., Arenas, J., Lucia, A., Vissing, J., Krag, T., Pinós, T. :
Preclinical Research in Glycogen Storage Diseases: A Comprehensive Review of Current Animal Models. Int J Mol Sci 21:, 2020. Pubmed reference: 33348688. DOI: 10.3390/ijms21249621.
2019 Kang, H.R., Gjorgjieva, M., Smith, S.N., Brooks, E.D., Chen, Z., Burgess, S.M., Chandler, R.J., Waskowicz, L.R., Grady, K.M., Li, S., Mithieux, G., Venditti, C.P., Rajas, F., Koeberl, D.D. :
Pathogenesis of Hepatic Tumors following Gene Therapy in Murine and Canine Models of Glycogen Storage Disease. Mol Ther Methods Clin Dev 15:383-391, 2019. Pubmed reference: 31890731. DOI: 10.1016/j.omtm.2019.10.016.
2018 Brooks, E.D., Landau, D.J., Everitt, J.I., Brown, T.T., Grady, K.M., Waskowicz, L., Bass, C.R., D'Angelo, J., Asfaw, Y.G., Williams, K., Kishnani, P.S., Koeberl, D.D. :
Long-term complications of glycogen storage disease type Ia in the canine model treated with gene replacement therapy. J Inherit Metab Dis :, 2018. Pubmed reference: 30043186. DOI: 10.1007/s10545-018-0223-y.
Lee, Y.M., Conlon, T.J., Specht, A., Coleman, K.E., Brown, L.M., Estrella, A.M., Dambska, M., Dahlberg, K.R., Weinstein, D.A. :
Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia. J Inherit Metab Dis 41:977-984, 2018. Pubmed reference: 29802554. DOI: 10.1007/s10545-018-0199-7.
2013 Brooks, E.D., Little, D., Arumugam, R., Sun, B., Curtis, S., Demaster, A., Maranzano, M., Jackson, M.W., Kishnani, P., Freemark, M.S., Koeberl, D.D. :
Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia. Mol Genet Metab :, 2013. Pubmed reference: 23623482. DOI: 10.1016/j.ymgme.2013.03.018.
2012 Demaster, A., Luo, X., Curtis, S., Williams, K.D., Landau, D.J., Drake, E.J., Kozink, D.M., Bird, A., Crane, B., Sun, F., Pinto, C.R., Brown, T.T., Kemper, A.R., Koeberl, D.D. :
Long-term efficacy following readministration of an adeno-associated virus vector in dogs with glycogen storage disease type Ia. Hum Gene Ther 23:407-18, 2012. Pubmed reference: 22185325. DOI: 10.1089/hum.2011.106.
Koeberl, D.D. :
In search of proof-of-concept: gene therapy for glycogen storage disease type Ia. J Inherit Metab Dis 35:671-8, 2012. Pubmed reference: 22310927. DOI: 10.1007/s10545-012-9454-5.
2011 Crane, B., Luo, X., Demaster, A., Williams, KD., Kozink, DM., Zhang, P., Brown, TT., Pinto, CR., Oka, K., Sun, F., Jackson, MW., Chan, L., Koeberl, DD. :
Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia. Gene Ther :, 2011. Pubmed reference: 21654821. DOI: 10.1038/gt.2011.86.
Specht, A., Fiske, L., Erger, K., Cossette, T., Verstegen, J., Campbell-Thompson, M., Struck, MB., Lee, YM., Chou, JY., Byrne, BJ., Correia, CE., Mah, CS., Weinstein, DA., Conlon, TJ. :
Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease. J Biomed Biotechnol 2011:646257, 2011. Pubmed reference: 21318173. DOI: 10.1155/2011/646257.
2010 Weinstein, DA., Correia, CE., Conlon, T., Specht, A., Verstegen, J., Onclin-Verstegen, K., Campbell-Thompson, M., Dhaliwal, G., Mirian, L., Cossette, H., Falk, DJ., Germain, S., Clement, N., Porvasnik, S., Fiske, L., Struck, M., Ramirez, HE., Jordan, J., Andrutis, K., Chou, JY., Byrne, BJ., Mah, CS. :
Adeno-associated virus-mediated correction of a canine model of glycogen storage disease type Ia. Hum Gene Ther 21:903-10, 2010. Pubmed reference: 20163245. DOI: 10.1089/hum.2009.157.
2009 Koeberl, D.D., Pinto, C., Brown, T., Chen, Y.T. :
Gene therapy for inhereted metabolic disorders in companion animals. ILAR J 50:122-7, 2009. Pubmed reference: 19293457.
2008 Koeberl, DD., Pinto, C., Sun, B., Li, S., Kozink, DM., Benjamin, DK., Demaster, AK., Kruse, MA., Vaughn, V., Hillman, S., Bird, A., Jackson, M., Brown, T., Kishnani, PS., Chen, YT. :
AAV vector-mediated reversal of hypoglycemia in canine and murine glycogen storage disease type Ia. Mol Ther 16:665-72, 2008. Pubmed reference: 18362924. DOI: 10.1038/mt.2008.15.
2002 Beaty, R.M., Jackson, M., Peterson, D., Bird, A., Brown, T., Benjamin, D.K., Juopperi, T., Kishnani, P., Boney, A., Chen, Y.T., Koeberl, D.D. :
Delivery of glucose-6-phosphatase in a canine model for glycogen storage disease, type Ia, with adeno-associated virus (AAV) vectors Gene Therapy 9:1015-1022, 2002. Pubmed reference: 12101432. DOI: 10.1038/
2001 Kishnani, P.S., Faulkner, E., VanCamp, S., Jackson, M., Brown, T., Boney, A., Koeberl, D., Chen, Y.T. :
Canine model and genomic structural organization of glycogen storage disease type Ia (GSD Ia) Veterinary Pathology 38:83-91, 2001. Pubmed reference: 11199168.
1997 Kishnani, P.S., Bao, Y., Wu, J.Y., Brix, A.E., Lin, J.L., Chen, Y.T. :
Isolation and nucleotide sequence of canine glucose-6-phosphatase mRNA: identification of mutation in puppies with glycogen storage disease type Ia. Biochem Mol Med 61:168-77, 1997. Pubmed reference: 9259982.
1995 Brix, A.E., Howerth, E.W., Mcconkierosell, A., Peterson, D., Egnor, D., Wells, M.R., Chen, Y.T. :
Glycogen storage disease type Ia in two littermate maltese puppies Veterinary Pathology 32:460-465, 1995. Pubmed reference: 8578635.

Edit History

  • Created by Frank Nicholas on 12 Sep 2005
  • Changed by Vicki Meyers-Wallen on 10 Sep 2011
  • Changed by Vicki Meyers-Wallen on 14 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 03 Sep 2012