Purine catabolism: purine nucleoside phosphorylase deficiency: practice question

A Biochemistry 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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Biochemistry · Purine catabolism: purine nucleoside phosphorylase deficiency

Sample item

A 2-year-old boy has recurrent opportunistic infections, lymphopenia and neurological delay. Serum uric acid is 0.4 mg/dL, and an enzyme assay shows absent purine nucleoside phosphorylase. Which combination best explains the immunodeficiency and low uric acid?

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

The answer and the reasoning

B. Deoxyguanosine accumulates and is converted to dGTP, which is toxic to T cells

Purine nucleoside phosphorylase converts inosine and guanosine (and their deoxy forms) to hypoxanthine and guanine, which feed xanthine oxidase. When it is absent, deoxyguanosine builds up and is phosphorylated to dGTP in T cells, inhibiting ribonucleotide reductase and causing T-cell apoptosis, with relatively spared B cells. Less hypoxanthine and guanine means very low uric acid.

Option by option

  • A. Lack of HGPRT causes PRPP excess and overproduction of uric acid

    HGPRT is intact here, and its deficiency (Lesch-Nyhan syndrome) causes hyperuricaemia.

  • B. Deoxyguanosine accumulates and is converted to dGTP, which is toxic to T cells (correct)

    The dGTP-mediated T-cell toxicity and the metabolic block together explain both the infections and the hypouricaemia.

  • C. Uric acid crystals deposit in the thymus and lymph nodes and destroy lymphocytes

    Uric acid is low in this disorder, so crystal deposition does not occur.

  • D. Excess dATP from absent adenosine deaminase damages both T and B cells

    Accumulation of dATP is the mechanism in adenosine deaminase deficiency, a different enzyme, and affects B cells as well.

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 Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, Deoxyguanosine accumulates and is converted to dGTP, which is toxic to T cells. Purine nucleoside phosphorylase converts inosine and guanosine (and their deoxy forms) to hypoxanthine and guanine, which feed xanthine oxidase.

Why is "Lack of HGPRT causes PRPP excess and overproduction of uric acid" not the answer?

HGPRT is intact here, and its deficiency (Lesch-Nyhan syndrome) causes hyperuricaemia.

Why is "Uric acid crystals deposit in the thymus and lymph nodes and destroy…" not the answer?

Uric acid is low in this disorder, so crystal deposition does not occur.

Why is "Excess dATP from absent adenosine deaminase damages both T and B cells" not the answer?

Accumulation of dATP is the mechanism in adenosine deaminase deficiency, a different enzyme, and affects B cells as well.

What concept does this question test?

It tests Purine catabolism: purine nucleoside phosphorylase deficiency in Biochemistry. When it is absent, deoxyguanosine builds up and is phosphorylated to dGTP in T cells, inhibiting ribonucleotide reductase and causing T-cell apoptosis, with relatively spared B cells. Less hypoxanthine and guanine means very low uric acid.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. 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 Purine catabolism: purine nucleoside phosphorylase deficiency?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry 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.