A 35-year-old woman develops acute abdominal pain, ascending motor neuropathy, and psychiatric symptoms after starting oral contraceptives. Her urine turns dark on exposure to light. Elevated urinary porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) confirm acute intermittent porphyria (AIP). The deficient enzyme in AIP is:

• A ALA synthase
• B Porphobilinogen deaminase (hydroxymethylbilane synthase) ✓
• C Uroporphyrinogen III cosynthase
• D Ferrochelatase

Explanation

AIP is caused by approximately 50% reduction in porphobilinogen deaminase (PBGD), also called hydroxymethylbilane synthase. When heme demand increases (induced by OCP, drugs, fasting, or stress via upregulation of ALA synthase 1), the partial enzyme deficiency becomes rate-limiting and PBG accumulates along with its precursor ALA. Both ALA and PBG are neurotoxic; ALA is structurally similar to GABA and interferes with neuronal signaling, explaining the triad of abdominal pain, neuropathy, and psychiatric manifestations.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.