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.