Clinical biochemistry: alpha-1 antitrypsin deficiency: 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 · Clinical biochemistry: alpha-1 antitrypsin deficiency

Sample item

A 3-month-old infant has prolonged cholestatic jaundice. Serum protein electrophoresis shows a markedly reduced alpha-1 band, and the father, a smoker, has early-onset emphysema. Which mechanism explains the liver disease in the infant?

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

The answer and the reasoning

B. Misfolded Z protein polymerises within the hepatocyte endoplasmic reticulum

In PiZZ alpha-1 antitrypsin deficiency the mutant Z protein folds abnormally and polymerises within the hepatocyte ER, producing PAS-positive diastase-resistant globules and a toxic gain of function that causes neonatal cholestasis and cirrhosis. The lung disease results from a loss of anti-elastase activity. Smoking accelerates emphysema.

Option by option

  • A. Unopposed neutrophil elastase destroys the bile ducts

    Unopposed elastase explains emphysema and not the neonatal liver injury.

  • B. Misfolded Z protein polymerises within the hepatocyte endoplasmic reticulum (correct)

    Correct. Retention of polymers in the ER injures hepatocytes, while low plasma levels cause lung disease.

  • C. Failure of canalicular transport of conjugated bilirubin

    Canalicular transport defects describe Dubin-Johnson or progressive familial intrahepatic cholestasis, not this electrophoretic finding.

  • D. Autoimmune destruction of the small bile ducts

    Autoimmune duct destruction describes primary biliary cholangitis in adults.

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.

More Biochemistry questions

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is B, Misfolded Z protein polymerises within the hepatocyte endoplasmic reticulum. In PiZZ alpha-1 antitrypsin deficiency the mutant Z protein folds abnormally and polymerises within the hepatocyte ER, producing PAS-positive diastase-resistant globules and a toxic gain of function that causes neonatal cholestasis and cirrhosis.

Why is "Unopposed neutrophil elastase destroys the bile ducts" not the answer?

Unopposed elastase explains emphysema and not the neonatal liver injury.

Why is "Failure of canalicular transport of conjugated bilirubin" not the answer?

Canalicular transport defects describe Dubin-Johnson or progressive familial intrahepatic cholestasis, not this electrophoretic finding.

Why is "Autoimmune destruction of the small bile ducts" not the answer?

Autoimmune duct destruction describes primary biliary cholangitis in adults.

What concept does this question test?

It tests Clinical biochemistry: alpha-1 antitrypsin deficiency in Biochemistry. The lung disease results from a loss of anti-elastase activity. Smoking accelerates emphysema.

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 Clinical biochemistry: alpha-1 antitrypsin deficiency?

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.