Glycogen Storage Disease

Of the 4 glycogen storage diseases reported in dogs, types I and III directly affect the liver, causing massive hepatomegaly in young puppies. These disorders are characterized by excessive accumulation of glycogen in the liver and other organs. Accumulated glycogen is unavailable for conversion to glucose as a result of defective glycolytic enzyme activity.

Type Ia glycogen storage disease involves a deficiency of glucose-6-phosphatase and has been reported in toy-breed dogs, particularly Maltese. There is no known gender predilection, and transmission is autosomal recessive. Clinical signs include emaciation, stunted growth, abdominal distention due to massive hepatomegaly, depression, and weakness associated with severe hypoglycemia. Histologic lesions are also observed in renal tubular epithelium. These dogs develop lactate acidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Affected puppies usually progress to death or euthanasia by 60 days of age. A genetic test is available for type 1 disease in Maltese dogs.

Type III glycogen storage disease is caused by a deficiency in amylo-1,6-glucosidase and is reported in German Shepherds. There is no recognized gender predilection, and an autosomal recessive transmission is suspected. Clinical signs include abdominal distention due to hepatomegaly and mild hypoglycemia. Glycogen stores are notable in both liver and skeletal muscle.

Diagnosis of these disorders is made based on a high index of suspicion considering breed affiliation and symptomatic hypoglycemia. Abdominal radiography reveals hepatomegaly, and ultrasonography reveals hyperechoic hepatic parenchyma consistent with hepatic glycogen or lipid accumulation. Differential diagnosis includes other causes of juvenile hypoglycemia (including malnutrition, endoparasitism, transient fasting hypoglycemia in toy breeds, and portosystemic vascular malformations) and other causes of muscular weakness (including endocrinopathies, immune-mediated disorders, infectious diseases, hypokalemia, and neuromyopathies). Supportive care consists of fluid support, IV dextrose for management of hypoglycemic crisis, and control of hypoglycemia with frequent feedings of a high-carbohydrate diet. Diagnosis is confirmed by tissue enzyme analysis, confirmation of excess glycogen stores in liver tissue, or genetic testing. Prognosis is poor. Affected dogs and their parents should be eliminated from breeding programs.

Hepatic Amyloidosis

Amyloidosis is a familial disease of Abyssinian, Siamese, and Oriental short-hair cats and Chinese Shar-Pei dogs. Shar-Peis are more likely to demonstrate episodic fever and swollen hocks, with or without renal failure, but the liver may also be affected by diffuse amyloid deposition. Affected Abyssinian cats often present with clinical signs related to the kidneys or with complications associated with diffuse hepatic amyloidosis. Oriental short-hair and Siamese cats generally present with amyloid-related hepatic complications. Other conditions associated with hepatic amyloidosis include a diversity of chronic infections or antigen exposures (eg, coccidioidomycosis in dogs, cyclic hematopoiesis in Gray Collies, infusion of porcine insulin in dogs) and hypervitaminosis A in cats.

While animals may be asymptomatic for long intervals, clinical signs may include fever, lymphadenopathy, vomiting, inappetence, weight loss, PU/PD, jaundice, and hepatomegaly. Acute presentation for severe abdominal hemorrhage subsequent to liver lobe rupture usually leads to a diagnosis in Oriental short-hair and Siamese cats. Ultrasonography can often identify a developing hematoma at the site of liver lobe rupture. Aspiration of abdominal effusion confirms active hemorrhage. Diagnosis can be made by aspiration cytology if amyloid fibrils are retrieved. Otherwise, diagnosis is made by identifying amyloid deposits in a liver biopsy.

Colchicine and dimethyl sulfoxide have been used to slow progression of systemic amyloidosis in Shar-Peis and cats, with limited success. Anecdotally, hepatic amyloid has regressed in Shar Peis treated with colchicine (0.03 mg/kg/day, sid to every other day). Because familial amyloidosis is a progressive systemic disorder, prognosis is poor. Cats surviving acute, severe hepatic hemorrhage by aggressive use of blood component therapy subsequently succumb to renal amyloidosis. (Also see Amyloidosis.)

Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM