Glycogen storage disease
Three forms of glycogen storage disease have been recognized in dogs:
- GSD Ia (von Gierke disease) - toy breeds - caused by a deficiency of glucose-6-phosphatase
- GSD II
- GSD IIIa - Curly-Coated Retriever, German Shepherd - deficiency of amylo-1,6-glucosidase enzyme
- GSD IV
Without G6Pase activity, all endogenous glucose production is impaired as this critical enzyme catalyzes the final step of both gluconeogenesis and glycogenolysis. Consequently, circulating blood glucose levels cannot be increased in response to positive glucoregulatory stimuli leading to a condition characterized by fasting hypoglycemia, as well as accumulation of glycogen and fat, particularly within liver and kidney tissues. Shunting of glucose-6-phosphate (G6P) into alternative metabolic pathways results in lactic acidosis, hypertriglyceridemia, and hyperuricemia.
Liver and muscle damages are common features in GSD IIIa patients, and serum enzyme activities related to these organs are often elevated in the patients. High levels of glycogen are detected in liver biopsies from four months of age.
Biochemical analysis of blood usually shows elevated AST and ALT levels, hypercholesterolemia and lactic acidemia.
Affected dogs are often young (under two years of age) and present with failure to thrive, episodic exercise intolerance, collapse, lethargy, hepatomegaly, liver fibrosis and cirrhosis.
A differential diagnosis would include other storage diseases such as mucopolysaccharidosis, phosphofructokinase deficiency, chronic hepatitis of Bedlinton Terriers as well as ketoacidosis due to diabetes mellitus and other causes of hepatomegaly such as congestive heart failure.
Diagnosis is based on genetic testing performed on blood or saliva from dogs using PCR and direct sequencing of the exon mutation sequence.
Although nutritional therapy is effective in moderating disease, alternative therapies such as novel longer-acting starches and/or gene therapy strategies are attractive as they may provide significant improvements in quality of life.
Experimental gene therapy with double-stranded adeno-associated virus vectors encoding human glucose-6-phosphatase has shown promise at alleviating clinical symptoms in dogs.
Prognosis for this condition is poor and most dogs succumb to these diseases at a young age.
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