Biomolecules and enzymes: GPI anchor defect in PNH: 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 · Biomolecules and enzymes: GPI anchor defect in PNH

Sample item

A 28-year-old woman has episodic dark urine in the morning, venous thrombosis and pancytopenia. Flow cytometry shows loss of CD55 and CD59 on her red cells. Which defect underlies the disease?

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

The answer and the reasoning

D. Defective synthesis of glycosylphosphatidylinositol anchors from a somatic PIGA mutation

CD55 and CD59 are attached to the cell surface by GPI anchors. In paroxysmal nocturnal haemoglobinuria a somatic mutation of PIGA in a haematopoietic stem cell blocks GPI anchor synthesis, leaving red cells unprotected against complement lysis. Complement-mediated haemolysis explains the haemoglobinuria, and thrombosis is a major cause of death.

Option by option

  • A. Deficiency of glucose-6-phosphate dehydrogenase

    G6PD deficiency causes oxidant-induced haemolysis with Heinz bodies, and CD55/CD59 are normal.

  • B. Failure to add mannose 6-phosphate to lysosomal enzymes

    Absent mannose 6-phosphate tagging of lysosomal enzymes causes I-cell disease, not complement haemolysis.

  • C. Defective spectrin-ankyrin linkage of the red cell cytoskeleton

    Spectrin-ankyrin defects cause hereditary spherocytosis, in which CD55 and CD59 are present.

  • D. Defective synthesis of glycosylphosphatidylinositol anchors from a somatic PIGA mutation (correct)

    Correct. A PIGA mutation stops GPI anchor synthesis, so CD55 and CD59 are not displayed and complement lyses the cells.

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.

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Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is D, Defective synthesis of glycosylphosphatidylinositol anchors from a somatic PIGA mutation. CD55 and CD59 are attached to the cell surface by GPI anchors.

Why is "Deficiency of glucose-6-phosphate dehydrogenase" not the answer?

G6PD deficiency causes oxidant-induced haemolysis with Heinz bodies, and CD55/CD59 are normal.

Why is "Failure to add mannose 6-phosphate to lysosomal enzymes" not the answer?

Absent mannose 6-phosphate tagging of lysosomal enzymes causes I-cell disease, not complement haemolysis.

Why is "Defective spectrin-ankyrin linkage of the red cell cytoskeleton" not the answer?

Spectrin-ankyrin defects cause hereditary spherocytosis, in which CD55 and CD59 are present.

What concept does this question test?

It tests Biomolecules and enzymes: GPI anchor defect in PNH in Biochemistry. In paroxysmal nocturnal haemoglobinuria a somatic mutation of PIGA in a haematopoietic stem cell blocks GPI anchor synthesis, leaving red cells unprotected against complement lysis. Complement-mediated haemolysis explains the haemoglobinuria, and thrombosis is a major cause of death.

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 Biomolecules and enzymes: GPI anchor defect in PNH?

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.