A 3-year-old boy with pica and developmental delay has Hb 8 g/dL, MCV 70 fL, and prominent basophilic stippling on peripheral smear. Blood lead level is markedly elevated. Which two enzymes of heme synthesis does lead directly inhibit?

• A ALA synthase and ferrochelatase
• B Uroporphyrinogen III synthase and coproporphyrinogen oxidase
• C Porphobilinogen deaminase and uroporphyrinogen decarboxylase
• D ALA dehydratase and ferrochelatase ✓

Explanation

Lead inhibits two enzymes in the heme pathway: delta-aminolevulinic acid dehydratase, blocking condensation of ALA into porphobilinogen, and ferrochelatase, blocking insertion of iron into protoporphyrin IX. The resulting anemia is microcytic with basophilic stippling from ribosomal RNA remnants. ALA synthase is vitamin D6 dependent and rate limiting but is not a lead target, while the enzymes in options C and B are affected in the acute hepatic porphyrias.

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.