Vitamins and minerals: pseudohypoparathyroidism: 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 · Vitamins and minerals: pseudohypoparathyroidism

Sample item

A short 10-year-old with a round face, short fourth metacarpals and subcutaneous calcifications has tetany. Serum calcium is low, phosphate is high and PTH is markedly raised. Urinary cAMP does not rise after PTH infusion. What is the underlying defect?

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

The answer and the reasoning

D. Deficient Gs-alpha signalling downstream of the PTH receptor

Albright hereditary osteodystrophy with end-organ PTH resistance results from inactivating GNAS mutations that reduce Gs-alpha, so PTH cannot raise cAMP in the kidney. PTH is high rather than low, which separates this from hypoparathyroidism. The resistance explains the low calcium with high phosphate.

Option by option

  • A. Deficient renal 1-alpha-hydroxylase

    Defective 1-alpha-hydroxylation would give normal or raised urinary cAMP response to PTH and would not cause skeletal dysmorphism.

  • B. Activating mutation of the calcium-sensing receptor

    An activating calcium-sensing receptor mutation suppresses PTH and does not give a raised level.

  • C. Absent parathyroid tissue from a 22q11 deletion

    A 22q11 deletion causes hypoparathyroidism with low PTH.

  • D. Deficient Gs-alpha signalling downstream of the PTH receptor (correct)

    Correct. Poor Gs-alpha signalling makes target tissues resistant to PTH.

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 D, Deficient Gs-alpha signalling downstream of the PTH receptor. Albright hereditary osteodystrophy with end-organ PTH resistance results from inactivating GNAS mutations that reduce Gs-alpha, so PTH cannot raise cAMP in the kidney.

Why is "Deficient renal 1-alpha-hydroxylase" not the answer?

Defective 1-alpha-hydroxylation would give normal or raised urinary cAMP response to PTH and would not cause skeletal dysmorphism.

Why is "Activating mutation of the calcium-sensing receptor" not the answer?

An activating calcium-sensing receptor mutation suppresses PTH and does not give a raised level.

Why is "Absent parathyroid tissue from a 22q11 deletion" not the answer?

A 22q11 deletion causes hypoparathyroidism with low PTH.

What concept does this question test?

It tests Vitamins and minerals: pseudohypoparathyroidism in Biochemistry. PTH is high rather than low, which separates this from hypoparathyroidism. The resistance explains the low calcium with high phosphate.

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 Vitamins and minerals: pseudohypoparathyroidism?

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.