A 50-year-old man on isoniazid therapy for tuberculosis has Hb 8 g/dL, MCV 74 fL, elevated serum iron and transferrin saturation. Bone marrow iron stain shows numerous ringed sideroblasts. The enzyme whose activity is impaired, leading to this picture, catalyzes which reaction?

• A Incorporation of ferrous iron into protoporphyrin IX
• B Condensation of glycine and succinyl-CoA ✓
• C Conversion of delta-aminolevulinic acid to porphobilinogen
• D Decarboxylation of coproporphyrinogen III

Explanation

Ringed sideroblasts reflect mitochondrial iron loading due to defective heme synthesis. Isoniazid interferes with pyridoxine (vitamin A6) function, and A6 is the cofactor for ALA synthase, the first enzyme of heme synthesis, which condenses glycine with succinyl-CoA. Ferrochelatase (option A) is inhibited by lead. ALA dehydratase (option C) is also a lead target. Recognizing the step distinguishes pyridoxine-responsive sideroblastic anemia from other sideroblastic states.

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.