Peroxisomal disorders: Zellweger syndrome: 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 · Peroxisomal disorders: Zellweger syndrome

Sample item

A neonate has marked hypotonia, a high forehead, seizures, hepatomegaly and no feeding. Plasma very long chain fatty acids are raised and plasmalogens are low. What is the underlying defect?

ADeficiency of lysosomal beta-glucocerebrosidaseBDeficiency of mitochondrial carnitine palmitoyltransferase IICIsolated defect of the ABCD1 peroxisomal transporterDDefective peroxisome biogenesis with impaired import of matrix enzymes (PEX genes)

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

The answer and the reasoning

D. Defective peroxisome biogenesis with impaired import of matrix enzymes (PEX genes)

Zellweger syndrome is an autosomal recessive disorder of PEX genes, so functional peroxisomes are lacking and multiple peroxisomal pathways fail. Very long chain fatty acids accumulate, and plasmalogen and bile acid synthesis are impaired. It is more severe and earlier than single-enzyme peroxisomal disease.

Option by option

A. Deficiency of lysosomal beta-glucocerebrosidase
Glucocerebrosidase deficiency causes Gaucher disease and does not raise very long chain fatty acids.
B. Deficiency of mitochondrial carnitine palmitoyltransferase II
CPT II deficiency affects mitochondrial long chain oxidation and does not lower plasmalogens.
C. Isolated defect of the ABCD1 peroxisomal transporter
An ABCD1 defect causes X-linked adrenoleukodystrophy, which is X-linked and presents later.
D. Defective peroxisome biogenesis with impaired import of matrix enzymes (PEX genes) (correct)
Correct. Generalised failure of peroxisomal import explains the multisystem neonatal picture.

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 D, Defective peroxisome biogenesis with impaired import of matrix enzymes (PEX genes). Zellweger syndrome is an autosomal recessive disorder of PEX genes, so functional peroxisomes are lacking and multiple peroxisomal pathways fail.

Why is "Deficiency of lysosomal beta-glucocerebrosidase" not the answer?

Glucocerebrosidase deficiency causes Gaucher disease and does not raise very long chain fatty acids.

Why is "Deficiency of mitochondrial carnitine palmitoyltransferase II" not the answer?

CPT II deficiency affects mitochondrial long chain oxidation and does not lower plasmalogens.

Why is "Isolated defect of the ABCD1 peroxisomal transporter" not the answer?

An ABCD1 defect causes X-linked adrenoleukodystrophy, which is X-linked and presents later.

What concept does this question test?

It tests Peroxisomal disorders: Zellweger syndrome in Biochemistry. Very long chain fatty acids accumulate, and plasmalogen and bile acid synthesis are impaired. It is more severe and earlier than single-enzyme peroxisomal disease.

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 Peroxisomal disorders: Zellweger syndrome?

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.