Glycogen Storage Diseases

Glycogen storage diseases are at least 12 inherited storage diseases, characterized by excessive glycogen accumulation in  tissues, which in most cases can be controlled by dietary means. Most involve the liver, even if the enzymatic deficiency is not localized to the liver. The critical abnormality is an insufficient glucose production, with hypoglycemic episodes when blood glucose levels are not supported by an inflow of glucose from the intestinal tract. The glycogen storage can be localized in the heart, skeletal muscle, central nervous system, kidney, intestine &. Liver transplantation has been performed in type I, III and IV.

Type I  glycogenosis (Von Gierkes disease)
This is the most common glycogen storage disease, that involves the liver and the kidney, first described by von Gierke, in 1929 &. The inheritance is autosomal recessive. The glycogen storage is due to the glucose-6-phosphatase enzyme deficiency. The diagnosis should be suspected in a child with hepatomegaly and associated hypoglycemia, lactic acidosis, growth failure, hyperuricemia and elevated transaminases. If the glucagon test demonstrates an absent or minimal rising of blood glucose level, liver biopsy should be taken for histology, including histochemistry, glycogen and enzyme analysis. The disease is usually controlled by frequent glucose and starch feeding, avoidance of lactose and sucrose, and allopurinol administration. Some patients may have difficulty complying with dietary restrictions and, in the long term, the development of liver adenomas has been described &. These conditions may represent an indications to liver transplantation, which has been performed with complete resolution of the metabolic defect.

Type III glycogenosis (Cori ‘s disease)
The disease is due to the deficiency of the debranching enzyme (amylo-1,6 glucosidase), and was first described by Forbes and coworkers, in 1952 &, and by Cori and colleagues, in 1956 &. Clinically this form resembles type I glycogenosis. Tolerance to fructose and galactose is normal. Periportal fibrosis occurs, but cirrhosis is rare. The development of adenomas is possible. Hepatic transplantation may be indicated for the same clinical problems of type I disease.

Type IV glycogenosis (Andersen’s disease)
In this form, initially described by Andersen in 1956 & and also known as amylopectinosis, the deficiency of the branching enzyme 1,4-glucan-6-glycosyltransferase causes the deposition of abnormal glycogen in several tissues. Enzyme deficiency can be detected in skin fibroblasts, muscle, leukocytes and amniotic cells. Dietary management is not successful and liver transplantation is the only available option for patients with type IV glycogen storage disease who progress to liver cirrhosis $.