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.
Type
Journal articleSubject
Age FactorsAnimals
Biomarkers
Disease Models, Animal
Disease Progression
Dog Diseases
Dogs
Female
Glycogen
Glycogen Storage Disease Type III
Hepatomegaly
Liver
Liver Cirrhosis
Male
Muscle, Skeletal
Muscular Diseases
Species Specificity
Urolithiasis
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Show full item recordScholars@Duke
Priya Sunil Kishnani
Chen Family Distinguished Professor of Pediatrics
RESEARCH INTERESTS A multidisciplinary approach to care of individuals with genetic
disorders in conjunction with clinical and bench research that contributes to: 1)
An understanding of the natural history and delineation of long term complications
of genetic disorders with a special focus on liver Glycogen storage disorders, lysosomal
disorders with a special focus on Pompe disease, Down syndrome and hypophosphatasia2) )
The development of new therapies such
Baodong Sun
Associate Professor in Pediatrics
My overall research interests are finding effective treatment for human glycogen storage
diseases (GSDs) and other inherited metabolic disorders. My current research focuses
on identification of novel therapeutic targets and development of effective therapies
for GSD II (Pompe disease), GSD III (Cori disease), and GSD IV (Andersen disease)
using cellular and animal disease models. The main therapeutic approaches we are using
in our pre-clinical studie
Sarah Phyllis Young
Professor of Pediatrics
As a clinical biochemical geneticist and a director of the Duke Biochemical Genetics
laboratory, my research interests are focused on improving laboratory diagnostics
for rare inherited disorders of metabolism. I am actively involved in the development
of assays using mass spectrometry and other analytical techniques. My current research
on biomarkers for lysosomal storage disorders, such as Fabry and Pompe disease and
the mucopolysaccharidoses includes monitoring the response to novel ther
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