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Biochemistry · Nucleotide metabolism: neurological basis of Lesch-Nyhan syndrome
Sample itemA boy with HGPRT deficiency has a normal urate on allopurinol, yet his dystonia and self-biting continue. What is the best explanation?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
D. The neurological features arise from basal ganglia dopaminergic dysfunction, not urate
Lowering urate prevents gout and stones but does not reverse the neurobehavioural syndrome, which is linked to reduced dopamine in the basal ganglia from the enzyme deficiency itself. Allopurinol therefore does not cure the neurological disease.
Option by option
A. Allopurinol blocks hypoxanthine salvage in the brain
Allopurinol inhibits xanthine oxidase and does not block salvage enzymes; the brain lacks the salvage enzyme already.
B. Residual xanthine is neurotoxic and persists on allopurinol
Xanthine accumulation causes stones in some patients but has not been shown to be the cause of the brain disease.
C. Allopurinol raises PRPP and worsens the neurological damage
Allopurinol does not increase PRPP, and PRPP excess is not the proven cause of the brain disease.
D. The neurological features arise from basal ganglia dopaminergic dysfunction, not urate (correct)
Correct. The brain disease stems from the enzyme deficiency and dopaminergic loss rather than from high urate.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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