OMIA:000419-9615 : Glycogen storage disease II in Canis lupus familiaris (dog)

In other species: domestic cat , taurine cattle , indicine cattle (zebu) , sheep , Japanese quail

Categories: Lysosomal storage disease

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 232300 (trait) , 606800 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Also called Pompe disease, Pompe's disease, acid maltase deficiency, and generalised glycogenesis type II. A lysosomal storage disease in which there is a buildup (storage) of glycogen, due to the lack of the enzyme alpha-glucosidase, whose task is to break down glycogen into its constituent glucose molecules. Characterised by poor growth, incoordination, muscle weakness and eventual recumbency.

Species-specific symbol: GSDII

History: This canine disorder was first reported by Mostafa (1970), in a Swedish Lapland dog.

Molecular basis: Adopting the comparative candidate-gene approach (based on similarity of diagnostic signs with humans), Seppälä et al. (2013) sequenced the canine GAA gene (encoding acid α-glucosidase) in "two affected Finnish Lapphunds, their dam and an unrelated healthy 8-year-old Finnish Lapphund as control", revealing a causal nonsense mutation: a "c.2237G>A mutation leading to a premature stop codon at amino acid position 746", i.e. p.W746*. Using a cell line established decades ago from tongue tissue, the authors "were able to establish that one of the originally described Swedish Lapphunds with Pompe disease (born in 1979) was also homozygous for the same c.2237G>A mutation". Exactly the same mutation in the human GAA gene causes the same disease (see the MIM entry above).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Affected dogs exhibit regurgitation and recurrent vomiting of mucus. Constant panting, dyspnoea, dysphonia, and dysphagia are evident at 13 months (Seppälä et al., 2013). Loss of condition, progressive muscular weakness, and exercise intolerance may become apparent (Almodóvar-Payá et al., 2020). Glycogen storage disease II (GSD II) in dogs may lead to decreases in ALP, and increases in ALAT, BUN, and glucose levels (Walvoort et al., 1984). Biochemical studies demonstrated a severe deficiency of acid α-glucosidase activity in heart, skeletal muscle, and liver fibroblasts. Glycogen content was substantially elevated in the heart and skeletal muscle (Walvoort et al., 1982). Haematology shows increases in monocyte count and increases in mean platelet volume at 18 months (Seppälä et al., 2013). Radiographs of affected dogs show dilatation of the oesophagus and cardiac enlargement; ultrasound indicates liver changes (Seppälä et al., 2013). GSD II is often associated with clinical heart disease and myocardial hypertrophy (Walvoort et al., 1984). [IT thanks DVM student Jed Stevens, who provided the basis of this contribution in April 2022]

Pathology: Acid α-glucosidase is responsible for the degradation of glycogen to glucose in lysosomes. Dogs with GSD II are significantly deficient in active acid α-glucosidase, leading to the accumulation of glycogen inside lysosomes of the heart, skeletal muscle, and smooth muscle (Almodóvar-Payá et al., 2020). This excessive glycogen storage may lead to progressive muscular weakness, cardiac hypertrophy, cardio-respiratory failure, and death (Walvoort et al.,1985; Seppälä et al., 2013). A finding unique to GSD II in dogs is the megaoesophagus and its associated symptoms of regurgitation and vomiting (Seppälä et al., 2013). [IT thanks DVM student Jed Stevens, who provided the basis of this contribution in April 2022]

Prevalence: Seppälä et al. (2013) "screened 95 Finnish Lapphunds, 99 Lapponian Herders and 34 Swedish Lapphunds" for the c.2237G>A; p.W746* causal mutation, observing 5%, 2% and zero carriers, respectively. This mutation was not present in 304 dogs from 21 other breeds. The same authors state that they "identified carriers from Lapponian Herders although no affected cases have been reported in this breed".

Breeds: Finnish Lapphund (Dog) (VBO_0200523), Lapponian Herder (Dog) (VBO_0200814), Swedish Lapphund (Dog) (VBO_0201315).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
GAA glucosidase, alpha; acid Canis lupus familiaris 9 NC_051813.1 (2247757..2233266) GAA Homologene, Ensembl , NCBI gene

Variants

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.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Inferred EVA rsID Year Published PubMed ID(s) Acknowledgements
270 Finnish Lapphund (Dog) Swedish Lapphund (Dog) Glycogen storage disease II GAA nonsense (stop-gain) Naturally occurring variant CanFam3.1 9 g.1603730C>T c.2237G>A p.(W746*) 2013 23457621 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:000419-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

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 21:9621, 2020. Pubmed reference: 33348688. DOI: 10.3390/ijms21249621.
2015 Brooks, E.D., Koeberl, D.D. :
Large animal models and new therapies for glycogen storage disease. J Inherit Metab Dis 38:505-9, 2015. Pubmed reference: 25224826. DOI: 10.1007/s10545-014-9766-8.
2013 Seppälä, E.H., Reuser, A.J., Lohi, H. :
A nonsense mutation in the acid α-glucosidase gene causes Pompe disease in Finnish and Swedish Lapphunds. PLoS One 8:e56825, 2013. Pubmed reference: 23457621. DOI: 10.1371/journal.pone.0056825.
1993 Reuser, A.J.J. :
Molecular biology, therapeutic trials and animal models of lysosomal storage diseases - Type-II glycogenosis as an example. Annales de Biologie Clinique 51:218-219, 1993.
1985 Walvoort, HC. :
Glycogen storage disease type II in the Lapland dog. Vet Q 7:187-90, 1985. Pubmed reference: 3901497.
Walvoort, HC., Koster, JF., Reuser, AJ. :
Heterozygote detection in a family of Lapland dogs with a recessively inherited metabolic disease: canine glycogen storage disease type II. Res Vet Sci 38:174-8, 1985. Pubmed reference: 3923581.
Walvoort, HC., Dormans, JA., van den Ingh, TS. :
Comparative pathology of the canine model of glycogen storage disease type II (Pompe's disease). J Inherit Metab Dis 8:38-46, 1985. Pubmed reference: 3921759.
1984 Walvoort, HC., Slee, RG., Sluis, KJ., Koster, JF., Reuser, AJ. :
Biochemical genetics of the Lapland dog model of glycogen storage disease type II (acid alpha-glucosidase deficiency). Am J Med Genet 19:589-98, 1984. Pubmed reference: 6391168. DOI: 10.1002/ajmg.1320190323.
1983 Walvoort, HC. :
Glycogen storage diseases in animals and their potential value as models of human disease. J Inherit Metab Dis 6:3-16, 1983. Pubmed reference: 6408305.
1982 Walvoort, HC., Slee, RG., Koster, JF. :
Canine glycogen storage disease type II. A biochemical study of an acid alpha-glucosidase-deficient Lapland dog. Biochim Biophys Acta 715:63-9, 1982. Pubmed reference: 7041988.
1970 Mostafa, I.E. :
A case of glycogenic cardiomegaly in a dog. Acta Veterinaria Scandinavica 11:197-208, 1970. Pubmed reference: 5270856.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 17 May 2013
  • Changed by Imke Tammen2 on 02 Jun 2022
  • Changed by Imke Tammen2 on 03 Jun 2022