Von Gierke disease (GSD type Ia) is caused by glucose-6-phosphatase deficiency. The enzyme complex (G6Pase) is located on the luminal face of the ER membrane. Clinically, which laboratory finding is characteristic of this condition?

• A Elevated blood glucose, normal lactate, and elevated glycogen in liver
• B Hypoglycaemia with myoglobinuria after exercise only
• C Elevated blood glucose with ketonuria and no glycogen accumulation
• D Fasting hypoglycaemia with lactic acidaemia, hyperuricaemia, hypertriglyceridaemia, and elevated liver glycogen ✓

Explanation

In GSD Ia, G6Pase cannot dephosphorylate glucose-6-phosphate to free glucose for export. During fasting, G6P accumulates in hepatocytes: it cannot be released as glucose (hypoglycaemia), is converted to lactate via glycolysis (lactic acidaemia), drives ribose-5-phosphate and PRPP production increasing purine synthesis (hyperuricaemia), and is diverted to fatty acid/triglyceride synthesis (hypertriglyceridaemia, hepatic steatosis). Paradoxically, glycogen also accumulates because G6P stimulates glycogen synthesis. Hypoglycaemia with myoglobinuria after exercise characterises McArdle disease (GSD V — myophosphorylase deficiency). Elevated blood glucose is the opposite of what occurs.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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