Of the four 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, caused by deficiency of glucose-6-phosphatase-α, has been reported in toy-breed dogs, particularly Maltese. There is no gender predilection, and disease transmission is autosomal recessive. Clinical signs include emaciation, stunted growth, abdominal distention due to massive hepatomegaly (glycogen and lipid vacuolation of hepatocytes), and lethargy and weakness associated with severe hypoglycemia. Histologic lesions are also seen in renal tubular epithelium. Affected dogs develop lactic acidemia, hypercholesterolemia, hypertriglyceridemia, and hyperuricemia. Clinical signs 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, caused by a deficiency in glycogen debranching enzymes, has been reported in German Shepherds and Curly Coated Retrievers. There is no gender predilection, and an autosomal recessive transmission has been confirmed. Clinical signs include abdominal distention due to hepatomegaly and mild hypoglycemia. Glycogen stores are notable in both liver and skeletal muscle. In Curly Coated Retrievers, the mutation leads to profound hepatocyte glycogen vacuolation, resulting in progressive hepatic fibrosis and liver failure. Affected dogs also develop a progressive degenerative myopathy. A genetic test is available for type III disease in Curly Coated Retrievers.
Diagnosis of these disorders is 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 diagnoses include other causes of juvenile hypoglycemia (including malnutrition, endoparasitism, transient fasting hypoglycemia in toy breeds, and PSVAs) and other causes of muscular weakness (including endocrinopathies, immune-mediated disorders, infectious diseases, hypokalemia, and neuromyopathies). Supportive care consists of fluid support, IV dextrose to achieve euglycemia, and frequent feedings of a high-carbohydrate and protein diet. Diagnosis is confirmed by tissue enzyme analyses, 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.
Amyloidosis is a familial disease of Abyssinian, Siamese, and Oriental short-hair cats and Chinese Shar-Pei dogs. Affected Shar-Pei are more likely to demonstrate episodic fever and swollen hocks (Shar-Pei fever) 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 or amyloid deposition in other organs. 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.
Although 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 the 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; amyloid is confirmed by tissue staining with Congo red and examination under polarized light.
Because familial amyloidosis is a progressive systemic disorder, prognosis is poor. Cats surviving acute, severe hepatic hemorrhage by aggressive administration of blood component therapy subsequently succumb to renal amyloidosis. (Also see Amyloidosis.) Colchicine and dimethyl sulfoxide have been used to slow progression of systemic amyloidosis in Shar-Pei dogs and in cats, with limited success. Anecdotally, hepatic amyloid has regressed in Shar Pei treated with colchicine (0.03 mg/kg/day, daily to every other day). Longterm survival in Shar Pei demonstrating systemic signs of Shar-Pei fever is possible with early institution of colchicine therapy. In predisposed Shar Pei, a duplication mutation upstream of the hyaluronic acid synthase 2 (HAS2) gene amplifies production of hyaluronic acid, which initiates chronic inflammation and amyloid formation. Additional genetic studies have identified complex polygenic modifier genes.