A 55-year-old man on isoniazid therapy develops anemia with MCV 102 fL. Bone marrow examination shows erythroid hyperplasia with ringed sideroblasts, defined by iron-laden mitochondria encircling at least one third of the nucleus. Isoniazid causes this picture by interfering with which step?

• A Vitamin B12-dependent conversion of homocysteine to methionine
• B Pyridoxine-dependent synthesis of delta-aminolevulinic acid ✓
• C Ferrochelatase-mediated insertion of iron into protoporphyrin
• D Globin chain translation on ribosomes

Explanation

Sideroblastic anemia results from defective heme synthesis causing iron accumulation in mitochondrial ring formations around the erythroblast nucleus. Isoniazid acts as a pyridoxine (vitamin B6) antagonist, and pyridoxal phosphate is the cofactor for ALA synthase, the first and rate-limiting enzyme of heme synthesis. Ferrochelatase is blocked by lead, not isoniazid, and the B12 pathway produces megaloblasts without ringed sideroblasts.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.