A 4-year-old child living in an old house with peeling paint has microcytic anemia, abdominal colic, and a peripheral smear showing coarse basophilic stippling. Lead inhibits which two enzymes of heme synthesis?

• A ALA synthase and uroporphyrinogen decarboxylase
• B ALA dehydratase and ferrochelatase ✓
• C Ferrochelatase and coproporphyrinogen oxidase
• D ALA dehydratase and porphobilinogen deaminase

Explanation

Lead directly inhibits delta-aminolevulinic acid dehydratase, blocking condensation of ALA into porphobilinogen, and ferrochelatase, the final enzyme inserting iron into protoporphyrin IX. The result is microcytic anemia with elevated free erythrocyte protoporphyrin and basophilic stippling from ribosomal RNA aggregation. Uroporphyrinogen decarboxylase is inhibited in porphyria cutanea tarda, and ALA synthase is the rate limiting step regulated by heme, not a lead target.

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.