A 2-year-old girl is brought to the physician because of irritability and failure to thrive. Physical examination shows hepatomegaly. Laboratory studies show mild fasting hypoglycemia. A high-protein diet or intravenous administration of fructose results in an increased serum glucose concentration. Biopsy of hepatic tissue shows increased amounts of glycogen with short outer branches. The most likely cause of her condition is a defect in which of the following?

Question

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The symptoms and biopsy findings are consistent with Cori disease, which is caused by a deficiency in the debranching enzyme. This leads to the accumulation of glycogen with short outer branches.  The child is suffering from glycogen storage disease type III (GSDIII), which is also known as Cori disease, Forbes disease, or limit dextrinosis. This GSD results from defects in the gene encoding glycogen debrancher enzyme, also known as amylo- 1,6-glucosidase. Deficiency in glycogen-debranching activity causes hepatomegaly, ketotic hypoglycemia, hyperlipidemia, variable skeletal myopathy, and cardiomyopathy and results in short stature. Patients with both liver and muscle involvement have GSDIIIa and those with only liver involvement (~15% of GSDIII patients) are classified as GSDIIIb. Because hepatomegaly, hypoglycemia, hyperlipidemia, and growth retardation are common symptoms in both GSDI and GSDIII, it is difficult to initially determine from which disease an infant is suffering. Definitive diagnosis is made only by examining the structure of the glycogen in patients as well as assaying for the level of activity of the debranching enzyme.

A 2-Year-Old Girl Is Brought to the Physician Because of Irritability