ABSTRACT
Glycogen storage diseases or glycogenoses are inherited diseases caused by abnormalities of enzymes that regulate the synthesis or degradation of glycogen. Deleterious mutations in many genes of the glyco(geno)lytic or the glycogenesis pathways can potentially cause a glycogenosis, and currently mutations in fourteen different genes are known to cause animal or human glycogenoses, resulting in myopathies and/or hepatic disorders. The genetic bases of two forms of glycogenosis are currently known in horses. A fatal neonatal polysystemic type IV glycogenosis, inherited recessively in affected Quarter Horse foals, is due to a mutation in the glycogen branching enzyme gene (GBE1). A second type of glycogenosis, termed polysaccharide storage myopathy (PSSM), is observed in adult Quarter Horses and other breeds. A severe form of PSSM also occurs in draught horses. A mutation in the skeletal muscle glycogen synthase gene (GYS1) was recently reported to be highly associated with PSSM in Quarter Horses and Belgian draught horses. This GYS1 point mutation appears to cause a gain-of-function of the enzyme and to result in the accumulation of a glycogen-like, less-branched polysaccharide in skeletal muscle. It is inherited as a dominant trait. The aim of this work was to test for possible associations between genetic polymorphisms in four candidate genes of the glycogen pathway or the GYS1 mutation in Cob Normand draught horses diagnosed with PSSM by muscle biopsy.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/veterinary , Glycogen Synthase/genetics , Horse Diseases/genetics , 1,4-alpha-Glucan Branching Enzyme/genetics , Animals , Carbohydrate Metabolism, Inborn Errors/genetics , Carbohydrate Metabolism, Inborn Errors/pathology , Female , Genetic Predisposition to Disease , Glycogen Storage Disease/genetics , Glycogen Storage Disease/veterinary , Horse Diseases/pathology , Horses , Muscle, Skeletal/pathologyABSTRACT
Gluteus medius muscle was sampled from 53 Cob Normand horses for histologic evaluation. Twenty horses (38%) exhibited amylase-resistant material in myocytes consistent with polysaccharide storage myopathy. Diameter of affected type II fibers was increased (67.7 +/- 21.4 microm) compared with normal ones (57.3 +/- 19.7 microm). Two groups were distinguished by quantitative study. The first group (n = 14; 26%) was characterized by a low percentage of fibers (m = 0.98%) containing aggregates occurring singly or in perifascicular clusters without myopathic changes. The second group (n = 6; 11%) was characterized by a high percentage (m = 18.1%) of fibers containing aggregates scattered in biopsy with chronic myopathic changes. Re-biopsy of 4 horses showed an increase with time in the number of aggregate-containing fibers for horses of the first group only. In 1 necropsied horse, aggregates were observed in a wide range of muscles including smooth muscles. Ultrastructurally, granular material was found interspersed among arrays of filamentous material.
