Clinical biochemistry: Crigler-Najjar syndrome type I: 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 · Clinical biochemistry: Crigler-Najjar syndrome type I

Sample item

A newborn is deeply jaundiced from day 2, with unconjugated bilirubin above 25 mg/dL, normal liver enzymes, no haemolysis and a negative Coombs test. Phototherapy helps only temporarily, and phenobarbital does not lower bilirubin. What is the underlying defect?

APartly reduced UGT1A1 activity that phenobarbital inducesBAutoimmune destruction of red cells by warm antibodiesCComplete absence of UGT1A1 activityDDefective canalicular transport by the MRP2 protein

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

The answer and the reasoning

C. Complete absence of UGT1A1 activity

Crigler-Najjar type I is autosomal recessive, with no UGT1A1 activity and severe unconjugated hyperbilirubinaemia causing kernicterus risk. Phenobarbital cannot induce a missing enzyme, so lifelong phototherapy and liver transplantation are used. Type II has residual activity and responds to phenobarbital.

Option by option

A. Partly reduced UGT1A1 activity that phenobarbital induces
Residual activity that responds to phenobarbital is Crigler-Najjar type II.
B. Autoimmune destruction of red cells by warm antibodies
Autoimmune haemolysis is excluded by a negative Coombs test and no haemolysis.
C. Complete absence of UGT1A1 activity (correct)
Correct. Absent enzyme activity explains severe, phenobarbital-resistant hyperbilirubinaemia.
D. Defective canalicular transport by the MRP2 protein
MRP2 defects cause Dubin-Johnson syndrome with conjugated hyperbilirubinaemia.

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 C, Complete absence of UGT1A1 activity. Crigler-Najjar type I is autosomal recessive, with no UGT1A1 activity and severe unconjugated hyperbilirubinaemia causing kernicterus risk.

Why is "Partly reduced UGT1A1 activity that phenobarbital induces" not the answer?

Residual activity that responds to phenobarbital is Crigler-Najjar type II.

Why is "Autoimmune destruction of red cells by warm antibodies" not the answer?

Autoimmune haemolysis is excluded by a negative Coombs test and no haemolysis.

Why is "Defective canalicular transport by the MRP2 protein" not the answer?

MRP2 defects cause Dubin-Johnson syndrome with conjugated hyperbilirubinaemia.

What concept does this question test?

It tests Clinical biochemistry: Crigler-Najjar syndrome type I in Biochemistry. Phenobarbital cannot induce a missing enzyme, so lifelong phototherapy and liver transplantation are used. Type II has residual activity and responds to phenobarbital.

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 Clinical biochemistry: Crigler-Najjar syndrome type I?

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.