Genetic and metabolic disorders: Smith-Lemli-Opitz syndrome: practice question

A Pediatrics 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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Pediatrics · Genetic and metabolic disorders: Smith-Lemli-Opitz syndrome

Sample item

A newborn boy has microcephaly, ptosis, an upturned nose, syndactyly of the second and third toes, hypospadias and poor feeding. Plasma cholesterol is low and 7-dehydrocholesterol is raised. Which process is defective?

ALDL receptor mediated uptake of circulating cholesterolBPeroxisomal oxidation of very long chain fatty acidsCEgress of cholesterol from late endosomes and lysosomesDThe final step of cholesterol biosynthesis

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

The answer and the reasoning

D. The final step of cholesterol biosynthesis

Smith-Lemli-Opitz syndrome results from 7-dehydrocholesterol reductase deficiency, the last enzymatic step of cholesterol synthesis. Precursors build up and cholesterol is low. Dietary cholesterol supplementation is the mainstay of treatment.

Option by option

A. LDL receptor mediated uptake of circulating cholesterol
An LDL receptor defect raises plasma cholesterol, as in familial hypercholesterolaemia.
B. Peroxisomal oxidation of very long chain fatty acids
A peroxisomal oxidation defect raises very long chain fatty acids, as in Zellweger syndrome, and does not lower cholesterol.
C. Egress of cholesterol from late endosomes and lysosomes
Impaired cholesterol egress from endolysosomes causes Niemann-Pick type C, not low plasma cholesterol with a raised precursor.
D. The final step of cholesterol biosynthesis (correct)
Correct. Defective 7-dehydrocholesterol reductase blocks the final step, so the precursor rises and cholesterol falls.

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 Pediatrics question

What is the answer to this Pediatrics question?

The best answer is D, The final step of cholesterol biosynthesis. Smith-Lemli-Opitz syndrome results from 7-dehydrocholesterol reductase deficiency, the last enzymatic step of cholesterol synthesis.

Why is "LDL receptor mediated uptake of circulating cholesterol" not the answer?

An LDL receptor defect raises plasma cholesterol, as in familial hypercholesterolaemia.

Why is "Peroxisomal oxidation of very long chain fatty acids" not the answer?

A peroxisomal oxidation defect raises very long chain fatty acids, as in Zellweger syndrome, and does not lower cholesterol.

Why is "Egress of cholesterol from late endosomes and lysosomes" not the answer?

Impaired cholesterol egress from endolysosomes causes Niemann-Pick type C, not low plasma cholesterol with a raised precursor.

What concept does this question test?

It tests Genetic and metabolic disorders: Smith-Lemli-Opitz syndrome in Pediatrics. Precursors build up and cholesterol is low. Dietary cholesterol supplementation is the mainstay of treatment.

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 Genetic and metabolic disorders: Smith-Lemli-Opitz syndrome?

Memorise milestones and the vaccine schedule as tables and revise them often. Then use the flashcards and the other Pediatrics 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.