Clinical biochemistry: hypophosphatasia: 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 · Clinical biochemistry: hypophosphatasia

Sample item

An infant has poor bone mineralisation with rachitic changes, premature loss of deciduous teeth with intact roots, hypercalcaemia and an unusually low serum alkaline phosphatase. Which gene is mutated?

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

The answer and the reasoning

D. ALPL, encoding tissue-nonspecific alkaline phosphatase

Hypophosphatasia results from loss-of-function mutations in ALPL. Reduced alkaline phosphatase activity allows pyrophosphate, an inhibitor of mineralisation, to accumulate, causing rickets or osteomalacia despite normal calcium and phosphate. Low ALP with such features distinguishes it from rickets, where ALP is high.

Option by option

  • A. COL1A1, encoding the pro-alpha1 chain of type I collagen

    COL1A1 mutations cause osteogenesis imperfecta with normal or raised ALP.

  • B. CYP27B1, encoding renal 1-alpha-hydroxylase

    CYP27B1 mutations cause vitamin D-dependent rickets type 1 with high ALP and low calcium.

  • C. PHEX, encoding a phosphate-regulating endopeptidase

    PHEX mutations cause X-linked hypophosphataemic rickets with high ALP.

  • D. ALPL, encoding tissue-nonspecific alkaline phosphatase (correct)

    Correct. ALPL mutations lower alkaline phosphatase and impair mineralisation.

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, ALPL, encoding tissue-nonspecific alkaline phosphatase. Hypophosphatasia results from loss-of-function mutations in ALPL.

Why is "COL1A1, encoding the pro-alpha1 chain of type I collagen" not the answer?

COL1A1 mutations cause osteogenesis imperfecta with normal or raised ALP.

Why is "CYP27B1, encoding renal 1-alpha-hydroxylase" not the answer?

CYP27B1 mutations cause vitamin D-dependent rickets type 1 with high ALP and low calcium.

Why is "PHEX, encoding a phosphate-regulating endopeptidase" not the answer?

PHEX mutations cause X-linked hypophosphataemic rickets with high ALP.

What concept does this question test?

It tests Clinical biochemistry: hypophosphatasia in Biochemistry. Reduced alkaline phosphatase activity allows pyrophosphate, an inhibitor of mineralisation, to accumulate, causing rickets or osteomalacia despite normal calcium and phosphate. Low ALP with such features distinguishes it from rickets, where ALP is high.

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 Clinical biochemistry: hypophosphatasia?

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.