Question

What is the possible cause for gout in a patient who has a glucose-6-phosphatase deficiency?

• A. Increased synthesis of pentoses
• B. Increased accumulation of sorbitol
• C. Increased synthesis of glycerol
• D. Decreased function of Krebs cycle

Hint:

Trapped glucose-6-phosphate is shunted into the pentose phosphate pathway, raising PRPP and purine and uric acid production.

Answer 1

The Correct Option is A

Step 1: Understanding the Question.
Glucose-6-phosphatase deficiency is Von Gierke disease (glycogen storage disease type I). This enzyme normally converts glucose-6-phosphate to free glucose in the liver, the last step before glucose leaves the liver into the blood. The question asks why patients with this deficiency develop gout, that is too much uric acid.

Step 2: See what happens to glucose-6-phosphate when the enzyme is missing.
Since glucose-6-phosphate cannot be turned into free glucose, it piles up inside liver cells. This trapped glucose-6-phosphate gets pushed down other available pathways instead, mainly glycolysis and the pentose phosphate pathway (also called the hexose monophosphate shunt).

Step 3: Follow the pentose phosphate route to uric acid.
The pentose phosphate pathway converts glucose-6-phosphate into ribose-5-phosphate. Extra ribose-5-phosphate is then used to make more phosphoribosyl pyrophosphate (PRPP), the starting material for purine synthesis. More PRPP drives more purine synthesis, and purines break down into uric acid. This raises blood uric acid and causes gout.

Step 4: Add the second contributing factor.
Because the liver cannot release free glucose, the body also runs more glycolysis for energy, and this raises lactate. High lactate competes with uric acid for the same excretion route in the kidney tubules, so less uric acid is cleared out. Both the extra production, through pentose and purine synthesis, and the reduced clearance, through lactic acidosis, push uric acid levels up together.

Step 5: Rule out the other options.

(B) Increased accumulation of sorbitol: Sorbitol buildup is tied to the aldose reductase pathway seen in diabetes and galactosemia, not to glucose-6-phosphatase deficiency. Incorrect.

(C) Increased synthesis of glycerol: Glycerol synthesis is not the driver of high uric acid in this disease. Incorrect.

(D) Decreased function of Krebs cycle: The Krebs cycle is not the pathway linked to purine overproduction here. Incorrect.

Step 6: Final Answer.
The trapped glucose-6-phosphate gets shunted into the pentose phosphate pathway, raising ribose-5-phosphate and PRPP, which drives extra purine synthesis and uric acid production.
\[ \boxed{\text{Increased synthesis of pentoses}} \]
Note: the source answer key for this question did not list a lettered answer (it was left blank on the page). Option (A) is filled in here based on the standard, well established mechanism of high uric acid in glucose-6-phosphatase deficiency (Von Gierke disease).