A 35-year-old man of African descent develops recurrent hemolytic crises precipitated by antimalarials and fava beans. G6PD assay performed during crisis shows near-normal enzyme activity. What is the explanation for this diagnostic pitfall?

• A The Mediterranean variant G6PD Med produces false-normal results due to unstable substrate affinity
• B G6PD A- variant retains near-normal activity in young reticulocytes, which predominate during crisis-driven reticulocytosis ✓
• C G6PD deficiency affects only granulocytes, not erythrocytes, so red cell assays are normal
• D Oxidative hemolysis in G6PD deficiency occurs via a non-G6PD enzyme pathway during crisis

Explanation

The G6PD A- variant (common in sub-Saharan Africans) produces an enzyme with near-normal activity in young cells but rapid decay with red cell aging. During hemolytic crisis, older, severely G6PD-deficient cells are selectively destroyed; the resulting reticulocytosis floods the blood with young erythrocytes that still have adequate enzyme activity, falsely normalising the assay. Testing should be deferred 2–3 months post-crisis for accurate diagnosis. The Mediterranean variant (G6PD Med) is severely deficient in all cell ages and does not exhibit this reticulocyte interference.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.