A 4-year-old boy living in an old house with peeling paint has abdominal colic, constipation, and a wrist radiograph showing dense metaphyseal bands. Hemogram shows microcytic anemia and prominent basophilic stippling. Lead inhibits which two enzymes of heme synthesis?

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

Explanation

Lead directly inhibits delta-aminolevulinic acid dehydratase, causing accumulation of ALA, and ferrochelatase, blocking insertion of iron into protoporphyrin IX. The result is a sideroblastic, microcytic anemia with basophilic stippling from ribosomal aggregation. Uroporphyrinogen decarboxylase is the enzyme blocked in porphyria cutanea tarda, and ALA synthase is rate limiting but regulated by heme feedback rather than lead inhibition. Elevated free erythrocyte protoporphyrin and zinc protoporphyrin support the diagnosis.

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.