A 3-month-old infant presents with severe hypoglycemia after fasting, hepatomegaly, and lactic acidosis. Liver biopsy shows glycogen accumulation. Enzyme assay reveals absent glucose-6-phosphatase activity. Which metabolic consequence directly explains the lactic acidosis in this condition?

• A Absent glucokinase activity prevents hepatic glucose phosphorylation
• B Deficient GLUT-2 transporter prevents hepatocyte glucose export
• C Increased fatty acid oxidation generates acetyl-CoA that inhibits pyruvate dehydrogenase
• D Accumulation of glucose-6-phosphate shunts substrate into glycolysis, producing excess pyruvate and lactate ✓

Explanation

In Von Gierke disease (GSD type Ia), absent glucose-6-phosphatase traps glucose-6-phosphate inside hepatocytes. The accumulated G-6-P is channelled into glycolysis, generating pyruvate in excess, which is reduced to lactate — causing the characteristic hyperlactatemia. Lactic acidosis is thus a direct overflow consequence, not a secondary effect of fat oxidation. GLUT-2 and glucokinase defects are not part of GSD Ia pathophysiology.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.