Lipid metabolism: Niemann-Pick disease type C: 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 · Lipid metabolism: Niemann-Pick disease type C

Sample item

A 7-year-old with earlier neonatal jaundice and hepatosplenomegaly now has ataxia, dystonia, dysarthria and loss of voluntary vertical eye movement. Filipin staining of fibroblasts shows unesterified cholesterol trapped in late endosomes. Which protein is defective?

ALow-density lipoprotein receptorBNPC1, which exports cholesterol from late endosomes and lysosomesCAcid sphingomyelinaseDGlucocerebrosidase

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

The answer and the reasoning

B. NPC1, which exports cholesterol from late endosomes and lysosomes

Niemann-Pick type C is caused by mutations in NPC1 or NPC2 and is a disorder of intracellular cholesterol transport rather than sphingomyelinase deficiency. Cholesterol and glycolipids accumulate, and vertical supranuclear gaze palsy with ataxia and dystonia is the typical neurological picture.

Option by option

A. Low-density lipoprotein receptor
A defective LDL receptor causes familial hypercholesterolaemia, with high plasma LDL and no neurodegeneration.
B. NPC1, which exports cholesterol from late endosomes and lysosomes (correct)
Correct. NPC1 moves cholesterol out of late endosomes, and its loss traps unesterified cholesterol.
C. Acid sphingomyelinase
Acid sphingomyelinase deficiency causes Niemann-Pick A and B, with normal cholesterol trafficking.
D. Glucocerebrosidase
Glucocerebrosidase deficiency causes Gaucher disease, with glucosylceramide in macrophages and no gaze palsy.

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 B, NPC1, which exports cholesterol from late endosomes and lysosomes. Niemann-Pick type C is caused by mutations in NPC1 or NPC2 and is a disorder of intracellular cholesterol transport rather than sphingomyelinase deficiency.

Why is "Low-density lipoprotein receptor" not the answer?

A defective LDL receptor causes familial hypercholesterolaemia, with high plasma LDL and no neurodegeneration.

Why is "Acid sphingomyelinase" not the answer?

Acid sphingomyelinase deficiency causes Niemann-Pick A and B, with normal cholesterol trafficking.

Why is "Glucocerebrosidase" not the answer?

Glucocerebrosidase deficiency causes Gaucher disease, with glucosylceramide in macrophages and no gaze palsy.

What concept does this question test?

It tests Lipid metabolism: Niemann-Pick disease type C in Biochemistry. Cholesterol and glycolipids accumulate, and vertical supranuclear gaze palsy with ataxia and dystonia is the typical neurological picture.

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: Niemann-Pick disease type C?

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.