Protein trafficking: 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.

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Biochemistry · Protein trafficking: I-cell disease

Sample item

A 1-year-old child has coarse facial features, gingival hyperplasia, restricted joint movement, kyphosis and severe psychomotor delay. Plasma levels of several lysosomal enzymes are markedly raised, while intracellular levels are low. Which defect is responsible?

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

The answer and the reasoning

C. Failure to add mannose-6-phosphate to lysosomal enzymes in the Golgi, so they are secreted instead of reaching lysosomes

I-cell (mucolipidosis II) is due to deficiency of N-acetylglucosamine-1-phosphotransferase, which adds the mannose-6-phosphate marker to lysosomal enzymes in the cis-Golgi. Without the tag, enzymes are secreted into blood and the lysosomes fill with undegraded material, forming inclusions in fibroblasts. The finding of raised plasma lysosomal enzymes is characteristic.

Option by option

  • A. Failure to cleave the signal peptide from secretory proteins

    Signal peptide cleavage is required for entry to the endoplasmic reticulum, which is intact here.

  • B. Deficiency of a single lysosomal hydrolase, causing storage of one substrate

    A single hydrolase deficiency would not raise multiple enzymes in plasma.

  • C. Failure to add mannose-6-phosphate to lysosomal enzymes in the Golgi, so they are secreted instead of reaching lysosomes (correct)

    Loss of the mannose-6-phosphate signal causes mis-sorting of many enzymes.

  • D. Failure of lysosomal enzymes to fold in the endoplasmic reticulum

    Many enzymes are mis-sorted in this condition, which differs from a folding defect in a single enzyme.

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 C, Failure to add mannose-6-phosphate to lysosomal enzymes in the Golgi, so they are secreted instead of reaching lysosomes. I-cell (mucolipidosis II) is due to deficiency of N-acetylglucosamine-1-phosphotransferase, which adds the mannose-6-phosphate marker to lysosomal enzymes in the cis-Golgi.

Why is "Failure to cleave the signal peptide from secretory proteins" not the answer?

Signal peptide cleavage is required for entry to the endoplasmic reticulum, which is intact here.

Why is "Deficiency of a single lysosomal hydrolase, causing storage of one su…" not the answer?

A single hydrolase deficiency would not raise multiple enzymes in plasma.

Why is "Failure of lysosomal enzymes to fold in the endoplasmic reticulum" not the answer?

Many enzymes are mis-sorted in this condition, which differs from a folding defect in a single enzyme.

What concept does this question test?

It tests Protein trafficking: I-cell disease in Biochemistry. Without the tag, enzymes are secreted into blood and the lysosomes fill with undegraded material, forming inclusions in fibroblasts. The finding of raised plasma lysosomal enzymes is characteristic.

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 Protein trafficking: 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.