Glycogen branching enzyme deficiency in quarter horse foals.
Abstract: Seven related Quarter Horse foals that died by 7 weeks of age were examined for glycogen branching enzyme (GBE) deficiency. Clinical signs varied from stillbirth, transient flexural limb deformities, seizures, and respiratory or cardiac failure to persistent recumbency. Leukopenia (5 of 5 foals) as well as high serum creatine kinase (CK; 5 of 5), aspartate transaminase (AST; 4 of 4), and gamma glutamyl transferase (GGT; 5 of 5) activities were present in most foals, and intermittent hypoglycemia was present in 2 foals. 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 in amounts proportional to the foal's age at death. 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 by 30%, but liver and cardiac muscle glycogen concentrations were normal. Several glycolytic enzyme activities were normal, whereas GBE activity was virtually absent in cardiac and skeletal muscle, as well as in liver and peripheral blood cells of 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 determined by Western blot 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. Pedigree analysis also supported an autosomal recessive mode of inheritance. The affected foals have at least 2,600 half-siblings. Consequently, GBE deficiency may be a common cause of neonatal mortality in Quarter Horses that is obscured by the variety of clinical signs that resemble other equine neonatal diseases.
Publication Date: 2002-01-31 PubMed ID: 11817063DOI: 10.1892/0891-6640(2001)0152.3.co;2Google Scholar: Lookup
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Summary
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The research article discusses the occurrence and investigation of Glycogen Branching Enzyme (GBE) deficiency in seven Quarter Horse foals, highlighting the varying clinical signs, the biochemical analysis of tissues, and genetic implications of this disorder. The study suggests that GBE deficiency could be a significant cause of neonatal horse mortality, often misdiagnosed due to the diverse clinical symptoms.
Research Background and Purpose
- The research was conducted after observing the unusual high death rate among Quarter Horse foals by the age of seven weeks. The researchers noticed clinical signs ranging from stillbirth, seizures, and respiratory or cardiovascular failure to continual lying down (recumbency).
- The purpose of the study was to examine the potential cause of these signs, specifically looking at the possible deficiency of a crucial enzyme known as the Glycogen Branching Enzyme (GBE).
Methods and Findings
- Several clinical tests were carried out on the foals, revealing leukopenia (low white blood cell count), along with high levels of serum creatine kinase (CK), aspartate transaminase (AST), and gamma glutamyl transferase (GGT) in most foals. Two foals also had intermittent episodes of hypoglycemia (low blood sugar).
- Postmortem examinations noted minimal gross lesions but lung edema in two foals. Muscle, heart or liver samples exhibited abnormal globular or crystalline inclusions.
- A biochemistry-related test presented an accumulation of an unbranched polysaccharide, a complex carbohydrate, in the tissues of the foals. Further analysis stated that total polysaccharide concentrations in skeletal muscle were 30% less, but normal in the liver and heart.
- While levels of several glycolytic enzymes were normal, the activity of the GBE enzyme was virtually non-existent in various tissues, indicating GBE deficiency.
Genetic Connections and Implications
- The study found that GBE enzyme levels in the blood cells of the foals’ mothers and several of their half or full siblings were around 50% of the control level.
- By using Western blot, a technique to detect specific proteins, it was found that GBE proteins in the liver of the affected foals were significantly reduced or absent.
- Pedigree analysis of the horses supported that the lack of GBE occurs due to an autosomal recessive mode of inheritance, meaning that a horse can be a carrier for the deficiency without showing symptoms.
- The researchers raised concerns regarding the overall horse population, given that the affected foals have more than 2,600 half-siblings. They emphasized that GBE deficiency may be a significant, yet overlooked, cause of death in neonatal Quarter Horses due to the varied clinical symptoms.
Cite This Article
APA
Valberg SJ, Ward TL, Rush B, Kinde H, Hiraragi H, Nahey D, Fyfe J, Mickelson JR.
(2002).
Glycogen branching enzyme deficiency in quarter horse foals.
J Vet Intern Med, 15(6), 572-580.
https://doi.org/10.1892/0891-6640(2001)0152.3.co;2 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, USA. valbe001@tc.umn.edu
MeSH Terms
- 1,4-alpha-Glucan Branching Enzyme / analysis
- Abnormalities, Multiple / etiology
- Abnormalities, Multiple / veterinary
- Animals
- Animals, Newborn
- Blotting, Western
- Fatal Outcome
- Female
- Fetal Death / veterinary
- Glycogen Storage Disease Type III / genetics
- Glycogen Storage Disease Type III / pathology
- Glycogen Storage Disease Type III / veterinary
- Horse Diseases / genetics
- Horse Diseases / pathology
- Horses
- Male
- Muscle, Skeletal / pathology
- Pedigree
- Respiratory Insufficiency / etiology
- Respiratory Insufficiency / veterinary
- Seizures / etiology
- Seizures / veterinary
- Tissue Distribution
Citations
This article has been cited 15 times.- De Coster T, Zhao Y, Tšuiko O, Demyda-Peyrás S, Van Soom A, Vermeesch JR, Smits K. Genome-wide equine preimplantation genetic testing enabled by simultaneous haplotyping and copy number detection. Sci Rep 2024 Jan 23;14(1):2003.
- Koeberl DD, Koch RL, Lim JA, Brooks ED, Arnson BD, Sun B, Kishnani PS. Gene therapy for glycogen storage diseases. J Inherit Metab Dis 2024 Jan;47(1):93-118.
- Almodóvar-Payá A, Villarreal-Salazar M, de Luna N, Nogales-Gadea G, Real-Martínez A, Andreu AL, Martín MA, 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 2020 Dec 17;21(24).
- Corley KTT. Metabolic disorders in foals. Equine Vet Educ 2012 Aug;24(8):392-395.
- Aleman M, Costa LRR, Crowe C, Kass PH. Presumed Neuroglycopenia Caused by Severe Hypoglycemia in Horses. J Vet Intern Med 2018 Sep;32(5):1731-1739.
- Pinn TL, Divers TJ, Southard T, De Bernardis NP, Wakshlag JJ, Valberg S. Persistent hypoglycemia associated with lipid storage myopathy in a paint foal. J Vet Intern Med 2018 Jul;32(4):1442-1446.
- Maile CA, Hingst JR, Mahalingan KK, O'Reilly AO, Cleasby ME, Mickelson JR, McCue ME, Anderson SM, Hurley TD, Wojtaszewski JFP, Piercy RJ. A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase. Biochim Biophys Acta Gen Subj 2017 Jan;1861(1 Pt A):3388-3398.
- Orhan Akman H, Emmanuele V, Kurt YG, Kurt B, Sheiko T, DiMauro S, Craigen WJ. A novel mouse model that recapitulates adult-onset glycogenosis type 4. Hum Mol Genet 2015 Dec 1;24(23):6801-10.
- Akman HO, Sheiko T, Tay SK, Finegold MJ, Dimauro S, Craigen WJ. Generation of a novel mouse model that recapitulates early and adult onset glycogenosis type IV. Hum Mol Genet 2011 Nov 15;20(22):4430-9.
- Brosnahan MM, Brooks SA, Antczak DF. Equine clinical genomics: A clinician's primer. Equine Vet J 2010 Oct;42(7):658-70.
- Pal K, Kumar S, Sharma S, Garg SK, Alam MS, Xu HE, Agrawal P, Swaminathan K. Crystal structure of full-length Mycobacterium tuberculosis H37Rv glycogen branching enzyme: insights of N-terminal beta-sandwich in substrate specificity and enzymatic activity. J Biol Chem 2010 Jul 2;285(27):20897-903.
- Brooks SA, Gabreski N, Miller D, Brisbin A, Brown HE, Streeter C, Mezey J, Cook D, Antczak DF. Whole-genome SNP association in the horse: identification of a deletion in myosin Va responsible for Lavender Foal Syndrome. PLoS Genet 2010 Apr 15;6(4):e1000909.
- Bruno C, Cassandrini D, Assereto S, Akman HO, Minetti C, Di Mauro S. Neuromuscular forms of glycogen branching enzyme deficiency. Acta Myol 2007 Jul;26(1):75-8.
- Fyfe JC, Kurzhals RL, Hawkins MG, Wang P, Yuhki N, Giger U, Van Winkle TJ, Haskins ME, Patterson DF, Henthorn PS. A complex rearrangement in GBE1 causes both perinatal hypoglycemic collapse and late-juvenile-onset neuromuscular degeneration in glycogen storage disease type IV of Norwegian forest cats. Mol Genet Metab 2007 Apr;90(4):383-92.
- 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 2004 Jul;15(7):570-7.
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