Glycogen Storage Disease Type III (GSD III)

Inherited metabolic disease resulting in accumulation of abnormal glycogen in different tissues of the body.

Cori Disease; Forbes Disease; Illingworth-Cori-Forbes Disease; Amylo-1,6-Glucosidase Debrancher Deficiency; Glycogenosis III; Debranching Enzyme Deficiency; Limit Dextrinosis.

Incidence of GSD type III in the United States and other countries is estimated to make up for 24% of all patients affected with GSD.

Autosomal recessive. The responsible defect has been mapped to 1p21.

Deficiency of amylo-1,6-debrancher enzyme, an enzyme found in all tissues, that converts glycogen to glucose-1,6-phosphate, resulting in accumulation of dextrin. The site of glycogen accumulation is primarily cytoplasmic. Disease results from generalized liver and muscle (GSD IIIa) or isolated (liver only) deficiency of glycogen debranching enzyme (GSD IIIb).

Low blood glucose levels, elevated glycogen content in red blood cells, and elevated levels of fat. Uric acid and lactic acid levels are usually normal. Liver biopsy shows inflammatory changes, significantly abnormally structured glycogen content, and deficiency of the debrancher enzyme. Biopsy of muscle shows an accumulation of abnormally structured glycogen in type IIIa.

Affected organs vary. Moderate-to-marked hepatomegaly. May have moderate hypotonia and cardiomegaly. Hypoglycemia is rare (but can be profound), occurring mainly after fasting periods. Hepatic or cardiac failure is rare. Normal mental development. May have recurrent pneumonia. Muscle weakness is commonly present in childhood and occasionally is severe. Often the liver returns to a normal size at puberty, although the enzyme defect persists and transition into hepatic cirrhosis and later hepatocellular carcinoma is a known complication. Survival to adulthood however is common.

Assess extent of cardiac or hepatic involvement. Assess extent of muscle weakness, which can become a prominant feature after puberty in GSD IIIa. Treat intercurrent infections.

No specific difficulties with anesthesia have been described. A bleeding tendency may be present, which contraindicates regional anesthesia (central block procedures). Although hypoglycemia is rarely a clinical problem, blood glucose concentrations should be measured in the perioperative period and intravenous dextrose-containing solutions given if required. Depending on the operation, prolonged mechanical ventilation may be required postoperatively in patients with predominant muscle weakness.

Muscle relaxants and drugs with prolonged sedative properties should be used cautiously in children with marked hypotonia. If cardiac function is reduced, agents should be selected to avoid further myocardial depression.

Other glycogen storage diseases.