Which of the following is characterized by a deficiency of glucose-6-phosphatase resulting in hepatomegaly, lactic acidosis, and severe fasting hypoglycemia?

• A. Type I—von Gierke disease
• B. Type II—Pompe disease
• C. Type III—Cori disease
• D. Type IV—Andersen disease

Answer: (A)

The key idea is a block in the final step of making glucose in the liver. When glucose-6-phosphatase is deficient, the liver cannot convert glucose-6-phosphate into free glucose for release into the bloodstream during fasting. That means you get severe fasting hypoglycemia because endogenous glucose production is impaired. The buildup of glucose-6-phosphate also drives glycolysis, producing lactate and leading to lactic acidosis. Additionally, glycogen accumulates in the liver, causing hepatomegaly. This combination—glucose-6-phosphatase deficiency with hepatomegaly, lactic acidosis, and severe fasting hypoglycemia—is characteristic of von Gierke disease.

Other glycogen storage disorders show different patterns. Pompe disease stems from a lysosomal enzyme deficiency and mainly affects muscle and heart rather than causing marked fasting hypoglycemia or lactic acidosis. Cori disease involves a debranching enzyme defect, which causes glycogen accumulation but typically presents with milder hypoglycemia and without the same prominent lactic acidosis. Andersen disease, due to a branching enzyme deficiency, leads to rapid liver disease and cirrhosis and often early fatal outcomes, rather than the classic severe fasting hypoglycemia with lactic acidosis seen here.