General pharmacology and pharmacokinetics: TPMT pharmacogenetics: practice question

A Pharmacology question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Pharmacology · General pharmacology and pharmacokinetics: TPMT pharmacogenetics

Sample item

A child with acute lymphoblastic leukaemia develops severe pancytopenia within weeks of starting a standard dose of mercaptopurine. Deficiency of which enzyme is the likely explanation?

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

B. Thiopurine methyltransferase

Thiopurine methyltransferase inactivates mercaptopurine and azathioprine. Genetic deficiency leaves more drug to form cytotoxic thioguanine nucleotides, causing profound marrow suppression. Testing before treatment or dose reduction is advised.

Option by option

  • A. Glucose-6-phosphate dehydrogenase

    G6PD deficiency causes haemolysis with oxidant drugs rather than marrow suppression.

  • B. Thiopurine methyltransferase (correct)

    Correct. Without this enzyme more active thioguanine nucleotides accumulate and suppress the marrow.

  • C. Cytochrome P450 2D6

    CYP2D6 variants alter codeine and tamoxifen activation, not thiopurine handling.

  • D. N-acetyltransferase 2

    N-acetyltransferase 2 acetylates isoniazid and hydralazine, not thiopurines.

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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Questions about this Pharmacology question

What is the answer to this Pharmacology question?

The best answer is B, Thiopurine methyltransferase. Thiopurine methyltransferase inactivates mercaptopurine and azathioprine.

Why is "Glucose-6-phosphate dehydrogenase" not the answer?

G6PD deficiency causes haemolysis with oxidant drugs rather than marrow suppression.

Why is "Cytochrome P450 2D6" not the answer?

CYP2D6 variants alter codeine and tamoxifen activation, not thiopurine handling.

Why is "N-acetyltransferase 2" not the answer?

N-acetyltransferase 2 acetylates isoniazid and hydralazine, not thiopurines.

What concept does this question test?

It tests General pharmacology and pharmacokinetics: TPMT pharmacogenetics in Pharmacology. Genetic deficiency leaves more drug to form cytotoxic thioguanine nucleotides, causing profound marrow suppression. Testing before treatment or dose reduction is advised.

How hard is this question?

We tag it as an application question: it asks you to use a fact on a patient or a finding. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study General pharmacology and pharmacokinetics: TPMT pharmacogenetics?

Learn drugs as classes, then the exception in each class that an examiner would pick. Then use the flashcards and the other Pharmacology questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.