title: Natural Progression of Canine Glycogen Storage Disease Type IIIa.
abstract: Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of glycogen debranching enzyme activity. Hepatomegaly, muscle degeneration, and hypoglycemia occur in human patients at an early age. Long-term complications include liver cirrhosis, hepatic adenomas, and generalized myopathy. A naturally occurring canine model of GSD IIIa that mimics the human disease has been described, with progressive liver disease and skeletal muscle damage likely due to excess glycogen deposition. In the current study, long-term follow-up of previously described GSD IIIa dogs until 32 mo of age (n = 4) and of family-owned GSD IIIa dogs until 11 to 12 y of age (n = 2) revealed that elevated concentrations of liver and muscle enzyme (AST, ALT, ALP, and creatine phosphokinase) decreased over time, consistent with hepatic cirrhosis and muscle fibrosis. Glycogen deposition in many skeletal muscles; the tongue, diaphragm, and heart; and the phrenic and sciatic nerves occurred also. Furthermore, the urinary biomarker Glc4, which has been described in many types of GSD, was first elevated and then decreased later in life. This urinary biomarker demonstrated a similar trend as AST and ALT in GSD IIIa dogs, indicating that Glc4 might be a less invasive biomarker of hepatocellular disease. Finally, the current study further demonstrates that the canine GSD IIIa model adheres to the clinical course in human patients with this disorder and is an appropriate model for developing novel therapies.
authors.affiliation: Division of Medical Genetics and Laboratory Animal Resources, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Brooks
authors.affiliation: Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Yi
authors.affiliation: Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Austin
authors.affiliation: Department of Pathology, Genzyme, a Sanofi Company, Framingham, Massachusetts, USA.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Thurberg
authors.affiliation: Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Young
authors.affiliation: Laboratory of Comparative Medical Genetics, Michigan State University, East Lansing, Michigan, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Fyfe
authors.affiliation: Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
authors.affiliation: Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina. baodong.sun@dm.duke.edu.
authors.forename: Baodong
authors.initials: B
authors.lastname: Sun
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004195:Disease Models, Animal; D018450:Disease Progression; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006010:Glycogen Storage Disease Type III / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D006529:Hepatomegaly / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D013045:Species Specificity; D052878:Urolithiasis / Q000378:metabolism / Q000473:pathology / Q000662:veterinary
chemical_list: D015415:Biomarkers; D006003:Glycogen