Ham's test (acidified serum lysis test) is classically positive in paroxysmal nocturnal hemoglobinuria (PNH). The underlying molecular defect causing erythrocyte sensitivity to complement is:

• A Germline deletion of complement factor H causing unregulated alternative pathway
• B Acquired IgM anti-I antibody activating classical complement pathway
• C Somatic mutation in PIG-A gene causing GPI-anchor biosynthesis defect with loss of CD55 and CD59 ✓
• D C3 convertase deficiency allowing excess C5b-9 membrane attack complex formation

Explanation

PNH results from a somatic mutation in the X-linked PIG-A gene in a hematopoietic stem cell, impairing synthesis of glycosylphosphatidylinositol (GPI) anchors. The two critical GPI-anchored complement regulatory proteins lost are CD55 (DAF, decay accelerating factor) and CD59 (protectin), leading to uncontrolled complement-mediated lysis. Complement factor H mutations cause atypical HUS, not PNH. Anti-I antibody is in cold agglutinin disease.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.