A 34-year-old battery factory worker has Hb 8.8 g/dL, MCV 74 fL, elevated serum iron and ferritin, and a peripheral smear showing coarse basophilic stippling. Bone marrow shows numerous ring sideroblasts. The enzyme whose inhibition explains this picture catalyses:

• A ALA dehydratase, blocking conversion of aminolaevulinic acid to porphobilinogen
• B Uroporphyrinogen decarboxylase, causing uroporphyrin accumulation
• C ALA synthase, the rate-limiting first step of haem synthesis
• D Ferrochelatase, preventing incorporation of iron into protoporphyrin IX ✓

Explanation

Lead inhibits ferrochelatase, so iron cannot be inserted into protoporphyrin IX, and iron accumulates in mitochondria surrounding the nucleus as ring sideroblasts. Inhibition of ALA dehydratase also occurs and raises urinary ALA, contributing to the neurotoxicity picture, but the sideroblastic morphology follows specifically from the ferrochelatase block. Uroporphyrinogen decarboxylase inhibition defines porphyria cutanea tarda, and ALA synthase defects cause X-linked sideroblastic anaemia, not lead toxicity.

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.