A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 12-year-old girl comes to the clinic with a grossly enlarged abdomen. She has a history of frequent episodes of weakness, sweating, and pallor that are eliminated by eating. Her development has been slow. She started to walk unassisted at 2 years and was not performing well at school. Physical examination reveals a blood pressure of 100/60 mm Hg, heart rate of 80/min, and temperature of 36.9°C (98.4℉). On physical examination, the liver is enlarged, firm, and palpable up to the pelvis. The spleen and kidney are not palpable. Laboratory investigation reveals low blood glucose and pH with high lactate, triglycerides, ketones, and free fatty acids. The liver biopsy revealed high glycogen content. Hepatic glycogen structure was normal. The enzyme assay performed on the biopsy tissue revealed very low glucose-6-phosphatase levels. What is the most likely diagnosis?
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A
Cori's diseaseIncorrect. Cori disease (debranching enzyme deficiency) produces abnormal glycogen with short outer branches; this patient's glycogen structure is normal.
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B
Pompe's diseaseIncorrect. Pompe disease (acid α-glucosidase) involves lysosomal glycogen accumulation with prominent cardiomegaly, hypotonia, and early death — not the described pattern.
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C
Von-Gierke's diseaseCorrect. Glucose-6-phosphatase deficiency causes Von Gierke disease, producing fasting hypoglycemia, lactic acidosis, and hepatomegaly with normal-structured glycogen.
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D
McArdle diseaseIncorrect. McArdle disease (muscle phosphorylase deficiency) causes exercise-induced muscle cramps and myoglobinuria, not hepatomegaly or fasting hypoglycemia.
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E
Hers diseaseIncorrect. Hers disease (hepatic phosphorylase deficiency, GSD VI) causes mild hepatomegaly and ketotic hypoglycemia but lacks the severe lactic acidosis and hyperlipidemia of Von Gierke; the very low glucose-6-phosphatase activity is diagnostic of GSD I, not VI.
↑ Tap an answer to reveal the reasoning
Answer: C. This child with hepatomegaly, fasting hypoglycemia (relieved by eating), lactic acidosis, hyperlipidemia, ketosis, and elevated free fatty acids has Von Gierke disease (glycogen storage disease type Ia), caused by deficiency of glucose-6-phosphatase. The biopsy confirmed normal-structured glycogen accumulation in the liver and low G6Pase activity — clinching the diagnosis.
Without G6Pase, glucose-6-phosphate cannot be dephosphorylated to glucose, so neither glycogenolysis nor gluconeogenesis can release free glucose into the blood, producing severe fasting hypoglycemia. The accumulated G6P is shunted into glycolysis (driving lactate production → lactic acidosis), the pentose phosphate pathway (increased uric acid via purine breakdown — gout), and lipogenesis (hypertriglyceridemia). Free fatty acid mobilization with ketogenesis follows the hypoglycemic state.
Clinical features include doll-like 'cherubic' face, protuberant abdomen from massive hepatomegaly, growth retardation, and delayed motor/cognitive development. Treatment is frequent feedings, cornstarch at night, and avoidance of fructose/galactose. Clinical pearl: in Cori disease (GSD III, debrancher), glycogen has abnormal short outer branches; in McArdle (GSD V, muscle phosphorylase) symptoms are exercise-induced muscle cramps; Pompe (GSD II, lysosomal acid α-glucosidase) features cardiomegaly and hypotonia.
**Why each option:**
**A.** Cori disease (debranching enzyme deficiency) produces abnormal glycogen with short outer branches; this patient's glycogen structure is normal.
**B.** Pompe disease (acid α-glucosidase) involves lysosomal glycogen accumulation with prominent cardiomegaly, hypotonia, and early death — not the described pattern.
**C.** Correct. Glucose-6-phosphatase deficiency causes Von Gierke disease, producing fasting hypoglycemia, lactic acidosis, and hepatomegaly with normal-structured glycogen.
**D.** McArdle disease (muscle phosphorylase deficiency) causes exercise-induced muscle cramps and myoglobinuria, not hepatomegaly or fasting hypoglycemia.