This is the answer and explanation for USMLE Question #21 from the Dr. Ray Makar Facebook page. Try it first, then check your answer below.
The Question
A 6-month-old infant has fasting hypoglycemia, a large liver, lactic acidosis, high uric acid and high triglycerides. Which enzyme is deficient?
A. Glucose-6-phosphatase
B. Lysosomal acid ฮฑ-glucosidase
C. Muscle glycogen phosphorylase
D. Debranching enzyme
Correct Answer: A. Glucose-6-phosphatase
This is von Gierke disease (glycogen storage disease type I). Glucose-6-phosphatase is the last step of both glycogenolysis and gluconeogenesis in the liver. Without it, the liver cannot release free glucose, so fasting causes severe hypoglycemia. Trapped glucose-6-phosphate is shunted into lactate, triglycerides and uric acid, and glycogen builds up in the liver and kidneys.
Why the Other Answers Are Wrong
- Lysosomal acid ฮฑ-glucosidase: Pompe disease (type II), with cardiomegaly and muscle weakness but normal blood glucose.
- Muscle glycogen phosphorylase: McArdle disease (type V), with exercise cramps and myoglobinuria, not hypoglycemia.
- Debranching enzyme: Cori disease (type III), similar to von Gierke but milder, with normal lactate.
High-Yield Pearl
Treatment of von Gierke disease: frequent oral glucose or cornstarch feeds and avoiding fructose and galactose. Remember the classic glycogen storage diseases: Very Poor Carbohydrate Metabolism (Von Gierke, Pompe, Cori, McArdle).
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