Glycogen branching enzyme deficiency in quarter horse foals

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 (AS T, 4 of 4), and gamma glutamyl transferase (GGT; 5 of 5) activities were pr esent 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 Schiffs (PAS)-positive globular or crystalline intracellular inclusio ns in amounts proportional to the foal's age at death. Accumulation of an u nbranched 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 re duced by 30%, but liver and cardiac muscle glycogen concentrations were nor mal. Several glycolytic enzyme activities were normal, whereas GBE activity was virtually absent in cardiac and skeletal muscle, as well as in liver a nd peripheral blood cells of affected foals. GBE activities in peripheral b lood cells of dams of affected foals and several of their half-siblings or fall siblings were similar to 50% of controls. GBE protein in liver determi ned by Western blot was markedly reduced to absent in affected foals, and i n a half-sibling of an affected foal, it was approximately one-half the amo unt of normal controls. Pedigreed analysis also supported an autosomal rece ssive mode of inheritance. The affected foals have at least 2,600 half-sibl ings. Consequently, GBE deficiency may be a common cause of neonatal mortal ity in Quarter Horses that is obscured by the variety of clinical signs tha t resemble other equine neonatal diseases.