Lipid metabolism: sitosterolaemia: 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 · Lipid metabolism: sitosterolaemia

Sample item

A child has tendon xanthomas and early atherosclerosis with normal or only mildly raised plasma cholesterol. Plant sterols such as sitosterol are markedly elevated and there is haemolytic anaemia. Which defect explains this?

AMutation of the ABCG5 or ABCG8 sterol transporterBGain-of-function mutation of PCSK9CMutation of the LDL receptorDDefective apolipoprotein B-100 binding to the LDL receptor

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

The answer and the reasoning

A. Mutation of the ABCG5 or ABCG8 sterol transporter

ABCG5 and ABCG8 form a heterodimer that pumps plant sterols and cholesterol from enterocytes back into the gut lumen and from hepatocytes into bile. When it fails, plant sterols are absorbed and accumulate, causing xanthomas and premature atherosclerosis. Ezetimibe, which blocks sterol uptake, is effective.

Option by option

A. Mutation of the ABCG5 or ABCG8 sterol transporter (correct)
Correct. Loss of the ABCG5/G8 efflux pump allows plant sterols to be absorbed and retained.
B. Gain-of-function mutation of PCSK9
PCSK9 gain-of-function raises LDL by degrading the LDL receptor, with no plant sterol accumulation.
C. Mutation of the LDL receptor
LDL receptor mutations cause familial hypercholesterolaemia with very high LDL, not high plant sterols.
D. Defective apolipoprotein B-100 binding to the LDL receptor
Defective apo B-100 binding gives a familial hypercholesterolaemia-like picture with raised LDL but normal plant sterols.

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.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is A, Mutation of the ABCG5 or ABCG8 sterol transporter. ABCG5 and ABCG8 form a heterodimer that pumps plant sterols and cholesterol from enterocytes back into the gut lumen and from hepatocytes into bile.

Why is "Gain-of-function mutation of PCSK9" not the answer?

PCSK9 gain-of-function raises LDL by degrading the LDL receptor, with no plant sterol accumulation.

Why is "Mutation of the LDL receptor" not the answer?

LDL receptor mutations cause familial hypercholesterolaemia with very high LDL, not high plant sterols.

Why is "Defective apolipoprotein B-100 binding to the LDL receptor" not the answer?

Defective apo B-100 binding gives a familial hypercholesterolaemia-like picture with raised LDL but normal plant sterols.

What concept does this question test?

It tests Lipid metabolism: sitosterolaemia in Biochemistry. When it fails, plant sterols are absorbed and accumulate, causing xanthomas and premature atherosclerosis. Ezetimibe, which blocks sterol uptake, is effective.

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 Lipid metabolism: sitosterolaemia?

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.