OMIA:000420-9796 : Glycogen storage disease IV in Equus caballus
In other species: domestic cat , dog
Categories: Homeostasis / metabolism phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 232500 (trait) , 607839 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2004
Cross-species summary: Glycogen storage disease caused by glycogen branching enzyme (GBE) deficiency
Species-specific name: Glycogen storage disease IV (GSD IV); glycogen storage disease (GSD); glycogen branching enzyme deficiency (GBED); amylopectinosis
Species-specific description: A deficiency in the glycogen branching enzyme (GBE1) is responsible for the autosomal recessive disease in American Quarter Horses initially identified as GSD and later termed GBED or Glycogen Storage Disease IV (GSD IV) after a homologous condition in people. This genetic mutation leads to the inability to mobilize glycogen leading to decreased levels of glucose in the blood and ultimately organ failure leading to death (Valberg et al., 2001; Ward et al., 2004).
[IT thanks Elizabeth Clark, working under the guidance of Professor Ernie Bailey, for contributions to this entry in April 2022]
Mapping: Ward et al. (2004): "We .... mapped the GBE1 gene to equine chromosome 26 (ECA26q12–q13) and confirmed it as a candidate gene for GSD IV by microsatellite marker allele association (Ward et al. 2003)."
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on biochemical and histopathological evidence relating to the homologous disorder in other species), Ward et al. (2004) showed that this disorder in American Quarter horses is due to a c.102C>A base substitution in exon 1 of the GBE1 gene encoding glycogen branching enzyme, resulting in a p.(Y34X) nonsense mutation.
Tryon et al. (2009) screened American Quarter horses and American Paint horses for likely causal variants for several conditions and identified that the GBE1 c.102C>A variant is present in the American Paint horse population.
Clinical features: Valberg et al. (2001) investigated “related Quarter Horse foals that died by 7 weeks of age … . Clinical signs varied from stillbirth, transient flexural limb deformities, seizures, and respiratory or cardiac failure to persistent recumbency. Leukopenia … as well as high serum creatine kinase … , aspartate transaminase … , and gamma glutamyl transferase … activities were present in most foals, and intermittent hypoglycemia was present in 2 foals.“
Pathology: Valberg et al. (2001): “Gross postmortem lesions were minor, except for pulmonary edema in 2 foals. Muscle, heart, or liver samples from the foals contained abnormal periodic acid Schiff's (PAS)-positive globular or crystalline intracellular inclusions … . Accumulation of an unbranched polysaccharide in tissues was suggested by a shift in the iodine absorption spectra of polysaccharide isolated from the liver and muscle of affected foals. Skeletal muscle total polysaccharide concentrations were reduced ... , but liver and cardiac muscle glycogen concentrations were normal. Several glycolytic enzyme activities were normal, whereas GBE activity was virtually absent in ... affected foals. GBE activities in peripheral blood cells of dams of affected foals and several of their half-siblings or full siblings were approximately 50% of controls. GBE protein in liver ... was markedly reduced to absent in affected foals, and in a half-sibling of an affected foal, it was approximately one-half the amount of normal controls.”
Breeds: American Paint (Horse) (VBO_0000897), Quarter Horse (Horse) (VBO_0001057).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|GBE1||glucan (1,4-alpha-), branching enzyme 1||Equus caballus||26||NC_009169.3 (8667550..8912224)||GBE1||Homologene, Ensembl , NCBI gene|
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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|
|322||American Paint (Horse) Quarter Horse (Horse)||Glycogen storage disease IV||GBE1||nonsense (stop-gain)||Naturally occurring variant||EquCab3.0||26||g.8667651C>A||c.102C>A||p.(Y34*)||NM_001081940.2; NP_001075409.1||rs3437568674||2004||15366377||The genomic position in EquCab3.0 was provided by Elizabeth Clark, working under the guidance of Professor Ernie Bailey in April 2022|
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.
|2023||Haughan, J., Ortved, K.F., Robinson, M.A. :|
|Administration and detection of gene therapy in horses: A systematic review. Drug Test Anal 15:143-162, 2023. Pubmed reference: 36269665 . DOI: 10.1002/dta.3394.|
|2022||Aleman, M., Scalco, R., Malvick, J., Grahn, R.A., True, A., Bellone, R.R. :|
|Prevalence of genetic mutations in horses with muscle disease from a neuromuscular disease laboratory. J Equine Vet Sci 118:104129, 2022. Pubmed reference: 36150530 . DOI: 10.1016/j.jevs.2022.104129.|
|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.|
|Pinzon-Arteaga, C., Snyder, M.D., Lazzarotto, C.R., Moreno, N.F., Juras, R., Raudsepp, T., Golding, M.C., Varner, D.D., Long, C.R. :|
|Efficient correction of a deleterious point mutation in primary horse fibroblasts with CRISPR-Cas9. Sci Rep 10:7411, 2020. Pubmed reference: 32366884 . DOI: 10.1038/s41598-020-62723-3.|
|2009||Tryon, RC., Penedo, MC., McCue, ME., Valberg, SJ., Mickelson, JR., Famula, TR., Wagner, ML., Jackson, M., Hamilton, MJ., Nooteboom, S., Bannasch, DL. :|
|Evaluation of allele frequencies of inherited disease genes in subgroups of American Quarter Horses. J Am Vet Med Assoc 234:120-5, 2009. Pubmed reference: 19119976 . DOI: 10.2460/javma.234.1.120.|
|2004||Ward, TL., Valberg, SJ., Adelson, DL., Abbey, CA., Binns, MM., Mickelson, JR. :|
|Glycogen branching enzyme (GBE1) mutation causing equine glycogen storage disease IV. Mamm Genome 15:570-7, 2004. Pubmed reference: 15366377 .|
|2003||Sponseller, B. T., Valberg, S. J., Ward, T. L., Fales-Williams, A. J., Mickelson, J. R. :|
|Muscular weakness and recumbency in a Quarter Horse colt due to glycogen branching enzyme deficiency. Equine Veterinary Education 15:182-188, 2003. DOI: https://doi.org/10.1111/j.2042-3292.2003.tb00240.x.|
|Ward, T.L., Valberg, S.J., Lear, T.L., Guérin, G., Milenkovic, D., Swinburne, J.E., Binns, M.M., Raudsepp, T., Skow, L., Chowdhary, B.P., Mickelson, J.R. :|
|Genetic mapping of GBE1 and its association with glycogen storage disease IV in American Quarter horses. Cytogenet Genome Res 102:201-6, 2003. Pubmed reference: 14970703 . DOI: 10.1159/000075749.|
|2001||Valberg, S.J., Ward, T.L., Rush, B., Kinde, H., Hiraragi, H., Nahey, D., Fyfe, J., Mickelson, J.R. :|
|Glycogen branching enzyme deficiency in quarter horse foals Journal of Veterinary Internal Medicine 15:572-580, 2001. Pubmed reference: 11817063 .|
|1999||Render, J.A., Common, R.S., Kennedy, F.A., Jones, M.Z., Fyfe, J.C. :|
|Amylopectinosis in fetal and neonatal Quarter Horses. Vet Pathol 36:157-60, 1999. Pubmed reference: 10098645 . DOI: 10.1354/vp.36-2-157.|
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