Glycoprotein processing: I-cell disease: 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.

Try it

Biochemistry · Glycoprotein processing: I-cell disease

Sample item

An infant has coarse facies, gingival hyperplasia, restricted joint movement and psychomotor retardation. Plasma lysosomal enzyme levels are high, and fibroblasts show dense inclusions. What is the defect?

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

The answer and the reasoning

D. Lack of N-acetylglucosamine-1-phosphotransferase, so mannose 6-phosphate is not added

I-cell disease (mucolipidosis II) results from deficient GlcNAc-1-phosphotransferase in the Golgi, so lysosomal enzymes are not tagged with mannose 6-phosphate and are secreted into blood instead of being targeted to lysosomes. Substrates accumulate in inclusion bodies in cells. This is why plasma levels of several lysosomal enzymes are raised.

Option by option

  • A. Absent alpha-L-iduronidase in lysosomes

    Absent iduronidase would reduce activity in plasma and leads to Hurler syndrome with excess urinary glycosaminoglycans.

  • B. Failure of N-linked glycosylation in the endoplasmic reticulum

    Failed N-glycosylation would not selectively produce high plasma lysosomal enzymes.

  • C. Absent signal peptidase in the endoplasmic reticulum

    Signal peptidase absence would stop processing of all secretory proteins, not a selective lysosomal targeting defect.

  • D. Lack of N-acetylglucosamine-1-phosphotransferase, so mannose 6-phosphate is not added (correct)

    Correct. Without the mannose 6-phosphate tag enzymes are secreted rather than sent to lysosomes.

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.

More Biochemistry questions

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, Lack of N-acetylglucosamine-1-phosphotransferase, so mannose 6-phosphate is not added. I-cell disease (mucolipidosis II) results from deficient GlcNAc-1-phosphotransferase in the Golgi, so lysosomal enzymes are not tagged with mannose 6-phosphate and are secreted into blood instead of being targeted to lysosomes.

Why is "Absent alpha-L-iduronidase in lysosomes" not the answer?

Absent iduronidase would reduce activity in plasma and leads to Hurler syndrome with excess urinary glycosaminoglycans.

Why is "Failure of N-linked glycosylation in the endoplasmic reticulum" not the answer?

Failed N-glycosylation would not selectively produce high plasma lysosomal enzymes.

Why is "Absent signal peptidase in the endoplasmic reticulum" not the answer?

Signal peptidase absence would stop processing of all secretory proteins, not a selective lysosomal targeting defect.

What concept does this question test?

It tests Glycoprotein processing: I-cell disease in Biochemistry. Substrates accumulate in inclusion bodies in cells. This is why plasma levels of several lysosomal enzymes are raised.

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 Glycoprotein processing: I-cell disease?

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.